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Front. Biol.    2016, Vol. 11 Issue (4) : 285-304    https://doi.org/10.1007/s11515-016-1415-1
REVIEW
New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins
Jian Li,Chun Guo,Nickolas Steinauer,Jinsong Zhang()
Department of Pharmacology and Physiology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA
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Abstract

BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein–protein interactions in elucidating the mechanisms of leukemia fusion proteins.

OBJECTIVE: In this review, we aim to summarize these new developments while also providing a historic overview of the related early studies.

METHODS: A total of 218 publications were reviewed in this article, a majority of which were published after 2004. We also downloaded 3D structures of AML1-ETO domains from Protein Data Bank and provided a systematic summary of their structures.

RESULTS: By reviewing the literature, we summarized early and recent findings on AML1-ETO, including its protein–protein interactions, transcriptional and leukemogenic mechanisms, as well as the recently reported involvement of ETO family corepressors in regulating the function of E2A-Pbx1.

CONCLUSION: While the recent development in genomic and structural studies has clearly demonstrated that the fusion proteins function by directly regulating transcription, a further understanding of the underlying mechanisms, including crosstalk with other transcription factors and cofactors, and the protein–protein interactions in the context of native proteins, may be necessary for the development of highly targeted drugs for leukemia therapy.
Keywords AML1-ETO      E2A-Pbx1      E-proteins      chromosomal translocation      transcription      leukemia     
Corresponding Author(s): Jinsong Zhang   
Just Accepted Date: 18 July 2016   Online First Date: 10 August 2016    Issue Date: 30 August 2016
 Cite this article:   
Jian Li,Chun Guo,Nickolas Steinauer, et al. New insights into transcriptional and leukemogenic mechanisms of AML1-ETO and E2A fusion proteins[J]. Front. Biol., 2016, 11(4): 285-304.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-016-1415-1
https://academic.hep.com.cn/fib/EN/Y2016/V11/I4/285
Fig.1  Schematic representations of domain organization of AML1-ETO, E2A-Pbx1, and the related wild-type proteins. RHD: runt homology domain. NHR1-4: nervy homology regions 1-4. NHR1 and NHR4 are also known as TAFH and MYND zinc fingers, respectively. AD1 and AD2: activation domains 1 and 2. DES: downstream ETO-interacting sequences, which includes a minimal binding sub-region named NHR2 binding (N2B) motif. HD: homeobox domain. bHLH: basic helix-loop-helix domain. The vertical dash lines depict the breakpoints during chromosomal translocation.
Fig.2  Domains of AML1-ETO and their interacting proteins. Biochemical studies have identified an array of AML1-ETO-interacting proteins, many of which bind to the conserved RHD and NHR domains of AML1 and ETO, respectively. Proteins bound to RHD include: CBFb (Meyers et al., 1995), AML1(Li et al., 2015a), C/EBPa (Zhang et al., 1996), C/EBPb (Tahirov et al., 2001), GATA1 (Elagib et al., 2003), Ets1 (Kim et al., 1999; Shrivastava et al., 2014; Shiina et al., 2015), PU.1 (Petrovick et al., 1998), MEF (Mao et al., 1999), LEF1 (Li et al., 2004), c-FOS/c-JUN(D’Alonzo et al., 2002), BSAP/PAX5 (Libermann et al., 1999), SMAD3(Jakubowiak et al., 2000), Sp1 (Wei et al., 2008). Some of the transcription factors may interact with AML1-ETO indirectly through the proximal binding sites on target DNA. Proteins bound to the ETO portion of the fusion protein include: Atrophin-1 (Wood et al., 2000), Dnmt1 (Liu et al., 2005), SHARP (Salat et al., 2008), JMJD1c (Chen et al., 2015), PLZF (Melnick et al., 2000), Bcl6 (Chevallier et al., 2004), HEB/E2A/LYL1/LMO2/Ldb1(Sun et al., 2013), Gfi1 (McGhee et al., 2003), corepressors NCoR/SMRT/HDAC3, mSin3A/HDAC1/2 (Gelmetti et al., 1998; Lutterbach et al., 1998b; Wang et al., 1998; Amann et al., 2001; Hildebrand et al., 2001; Zhang et al., 2001), p300 (Wang et al., 2011a), HSP90 (Komori et al., 1999), ETO-2/MTGR1 (Kitabayashi et al., 1998; Liu et al., 2006), PKA(RIIa) (Fukuyama et al., 2001), and SON (Ahn et al., 2008). PRMT1 binds to AML1-ETO9a fragment (Shia et al., 2012). In addition to the reported binary interactions, proteome-scale mapping of the human interactome network further showed that ETO interacts with EPS8, MEOX2, STX11, ZMYM4, LPXN, HOMER3, SPRY2, MID2, GSE1, ABI3, TAF9B, WBP11, NECAB2, PRDM14, C19orf57, CPSF7, EFHC2, LZTS2, CREB3L1, SPERT, TRIM42, CCDC36, CEP170P1 (Rual et al., 2005; Rolland et al., 2014). Proteins that have been shown to involve direct interactions are highlighted in dark red.
Repression Molecular/Biological functions References
C/EBPa Transcription factor, myeloid differentiation Pabst et al., 2001
PIRIN Transcription factor, myeloid differentiation Licciulli et al., 2010
P14 (ARF) Tumor suppressor Linggi et al., 2002
Neurofibromatosis-1 Tumor suppressor Yang et al., 2005
RASSF2 Tumor suppressor Samuel A Stoner, 2013
CD45 Negative regulator of JAK/STAT signaling Lo et al., 2012
Cathepsin G Protease, AML1-ETO degradation Jin et al., 2013
OGG1 DNA repair Alcalay et al., 2003
Activation Molecular/Biological functions References
JUP(g-Catenin) Wnt/b-Catenin signaling Muller-Tidow et al., 2004; Zheng et al., 2004; Tonks et al., 2007
JAGGED1 Notch signaling Alcalay et al., 2003
TRKA Nerve Growth Factor receptor Mulloy et al., 2005
ID1 Maintains HSC self-renewal Jankovic et al., 2007
P21/WAF1 HSC self-renewal Peterson et al., 2007
PONTIN Cell cycle progression Breig et al., 2014
BCL2 Apoptosis inhibitor Klampfer et al., 1996
BCL-xl Apoptosis inhibitor Chou et al., 2012
Tab.1  List of representative AML1-ETO target genes
Fig.3  ETO and E-protein interactions. Schematic representations showing domain structures of ETO and E-proteins, along with the three binding interfaces: NHR1/AD1, NHR2/DES and NHR1/DES (Guo et al., 2009). DES harbors the minimal sub-region that shows binding to NHR2 (N2B).
Fig.4  Differential involvement of ETO-corepressor/E-protein interactions in distinct leukemogenic pathways. (A) Alignment of PCET sequences from HEB, E2-2 and E2A. E2A-specific change is labeled with yellow stars. (B) In t(8;21) AML, strong AML1-ETO/E-protein (HEB or E2A) interactions facilitate transcriptional repression to promote leukemogenesis. (C) In t(1;19) ALL, due to E2A-specific amino-acid changes flanking the PCET motif, the binding affinity of E2A-Pbx1 to ETO-2/MTGR1 corepressors is reduced. As a result, E2A-Pbx1 is skewed toward recruiting p300/CBP HATs for gene activation.
Domain Structure description PDB number References
RHD RHD 1CO1, 1LJM, 1CMO Berardi et al., 1999; Nagata et al., 1999; Bartfeld et al., 2002
RHD+ DNA 1HJC Tahirov et al., 2001
RHD+ CBFb + C/EBPb + DNA 1IO4 Tahirov et al., 2001
RHD+ CBFb + DNA 1H9D Bravo et al., 2001
RHD+ CBFb 1E50 Warren et al., 2000
NHR1(eTAFH) NHR1 2H7B Plevin et al., 2006
NHR1 (F136Y) 2PP4 Wei et al., 2007
NHR1+ HEB-PCET 2KNH Park et al., 2009a
NHR2 NHR2 1WQ6 Liu et al., 2006
NHR2+ HEB-N2B 4JOL Sun et al., 2013
NHR3 NHR3+ PKA(RIIa) 2KYG Corpora et al., 2010
NHR4 NHR4 2OD1 Liu et al., 2007
NHR4+ SMRT 2ODD Liu et al., 2007
dTAFH TAF4-TAFH 2P6V Wang et al., 2007
Tab.2  Reported 3D structures of AML1-ETO domains
Fig.5  3D models of AML1-ETO and its complexes with binding partners. Available 3D structures of isolated AML1-ETO domains are shown by PyMOL and the structures were connected with dashed lines. RHD is colored in blue, its binding partner CBFb in cyan, NHR1 in green, NHR2 in orange, NHR3 in hot pink, and NHR4 in red. For ETO binding partners, HEB peptides are in yellow, PKA (RIIa) in gray, and SMRT peptide in pale cyan. Note that NHR2 mediates tetramerization of AML1-ETO proteins (the other three NHR2 domains are in gray), thus bridging 4 copies of each interacting proteins. AML-ETO can also form hetero-oligomers with ETO family proteins (ETO-2, MTGR1).
1 Ahn E Y, DeKelver R C, Lo M C, Nguyen T A, Matsuura S, Boyapati A, Pandit S, Fu X D, Zhang D E (2011). SON controls cell-cycle progression by coordinated regulation of RNA splicing. Mol Cell, 42(2): 185–198
https://doi.org/10.1016/j.molcel.2011.03.014 pmid: 21504830
2 Ahn E Y, Yan M, Malakhova O A, Lo M C, Boyapati A, Ommen H B, Hines R, Hokland P, Zhang D E (2008). Disruption of the NHR4 domain structure in AML1-ETO abrogates SON binding and promotes leukemogenesis. Proc Natl Acad Sci USA, 105(44): 17103–17108
https://doi.org/10.1073/pnas.0802696105 pmid: 18952841
3 Alcalay M, Meani N, Gelmetti V, Fantozzi A, Fagioli M, Orleth A, Riganelli D, Sebastiani C, Cappelli E, Casciari C, Sciurpi M T, Mariano A R, Minardi S P, Luzi L, Muller H, Di Fiore P P, Frosina G, Pelicci P G (2003). Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair. J Clin Invest, 112(11): 1751–1761
https://doi.org/10.1172/JCI17595 pmid: 14660751
4 Amann J M, Nip J, Strom D K, Lutterbach B, Harada H, Lenny N, Downing J R, Meyers S, Hiebert S W (2001). ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain. Mol Cell Biol, 21(19): 6470–6483
https://doi.org/10.1128/MCB.21.19.6470-6483.2001 pmid: 11533236
5 Anantharaman A, Lin I J, Barrow J, Liang S Y, Masannat J, Strouboulis J, Huang S, Bungert J (2011). Role of helix-loop-helix proteins during differentiation of erythroid cells. Mol Cell Biol, 31(7): 1332–1343
https://doi.org/10.1128/MCB.01186-10 pmid: 21282467
6 Arkin M R, Tang Y, Wells J A (2014). Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol, 21(9): 1102–1114
https://doi.org/10.1016/j.chembiol.2014.09.001 pmid: 25237857
7 Aspland S E, Bendall H H, Murre C (2001). The role of E2A-PBX1 in leukemogenesis. Oncogene, 20(40): 5708–5717
https://doi.org/10.1038/sj.onc.1204592 pmid: 11607820
8 Azzarito V, Long K, Murphy N S, Wilson A J (2013). Inhibition of a-helix-mediated protein-protein interactions using designed molecules. Nat Chem, 5(3): 161–173
https://doi.org/10.1038/nchem.1568 pmid: 23422557
9 Bain G, Engel I, Robanus Maandag E C, te Riele H P, Voland J R, Sharp L L, Chun J, Huey B, Pinkel D, Murre C (1997). E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas. Mol Cell Biol, 17(8): 4782–4791
https://doi.org/10.1128/MCB.17.8.4782 pmid: 9234734
10 Barbetti V, Gozzini A, Rovida E, Morandi A, Spinelli E, Fossati G, Mascagni P, Lübbert M, Dello Sbarba P, Santini V (2008). Selective anti-leukaemic activity of low-dose histone deacetylase inhibitor ITF2357 on AML1/ETO-positive cells. Oncogene, 27(12): 1767–1778
https://doi.org/10.1038/sj.onc.1210820 pmid: 17891169
11 Bartfeld D, Shimon L, Couture G C, Rabinovich D, Frolow F, Levanon D, Groner Y, Shakked Z (2002). DNA recognition by the RUNX1 transcription factor is mediated by an allosteric transition in the RUNT domain and by DNA bending. Structure, 10(10): 1395–1407
https://doi.org/10.1016/S0969-2126(02)00853-5 pmid: 12377125
12 Bayly R, Chuen L, Currie R A, Hyndman B D, Casselman R, Blobel G A, LeBrun D P (2004). E2A-PBX1 interacts directly with the KIX domain of CBP/p300 in the induction of proliferation in primary hematopoietic cells. J Biol Chem, 279(53): 55362–55371
https://doi.org/10.1074/jbc.M408654200 pmid: 15507449
13 Bayly R, Murase T, Hyndman B D, Savage R, Nurmohamed S, Munro K, Casselman R, Smith S P, LeBrun D P (2006). Critical role for a single leucine residue in leukemia induction by E2A-PBX1. Mol Cell Biol, 26(17): 6442–6452
https://doi.org/10.1128/MCB.02025-05 pmid: 16914730
14 Berardi M J, Sun C, Zehr M, Abildgaard F, Peng J, Speck N A, Bushweller J H (1999). The Ig fold of the core binding factor alpha Runt domain is a member of a family of structurally and functionally related Ig-fold DNA-binding domains. Structure, 7(10): 1247–1256
https://doi.org/10.1016/S0969-2126(00)80058-1 pmid: 10545320
15 Bravo J, Li Z, Speck N A, Warren A J (2001). The leukemia-associated AML1 (Runx1)—CBF beta complex functions as a DNA-induced molecular clamp. Nat Struct Biol, 8(4): 371–378
https://doi.org/10.1038/86264 pmid: 11276260
16 Breig O, Bras S, Martinez Soria N, Osman D, Heidenreich O, Haenlin M, Waltzer L (2014). Pontin is a critical regulator for AML1-ETO-induced leukemia. Leukemia, 28(6): 1271–1279
https://doi.org/10.1038/leu.2013.376 pmid: 24342949
17 Burel S A, Harakawa N, Zhou L, Pabst T, Tenen D G, Zhang D E (2001). Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation. Mol Cell Biol, 21(16): 5577–5590
https://doi.org/10.1128/MCB.21.16.5577-5590.2001 pmid: 11463839
18 Calabi F, Cilli V (1998). CBFA2T1, a gene rearranged in human leukemia, is a member of a multigene family. Genomics, 52(3): 332–341
https://doi.org/10.1006/geno.1998.5429 pmid: 9790752
19 Calabi F, Pannell R, Pavloska G (2001). Gene targeting reveals a crucial role for MTG8 in the gut. Mol Cell Biol, 21(16): 5658–5666
https://doi.org/10.1128/MCB.21.16.5658-5666.2001 pmid: 11463846
20 Chang K S, Fan Y H, Stass S A, Estey E H, Wang G, Trujillo J M, Erickson P, Drabkin H (1993). Expression of AML1-ETO fusion transcripts and detection of minimal residual disease in t(8;21)-positive acute myeloid leukemia. Oncogene, 8(4): 983–988
pmid: 8455949
21 Chen F E, Huang D B, Chen Y Q, Ghosh G (1998). Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA. Nature, 391(6665): 410–413
https://doi.org/10.1038/34956 pmid: 9450761
22 Chen J, Odenike O, Rowley J D (2010). Leukaemogenesis: more than mutant genes. Nat Rev Cancer, 10(1): 23–36
https://doi.org/10.1038/nrc2765 pmid: 20029422
23 Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R, Shi Y, Armstrong S A, Roeder R G (2015). JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes Dev, 29(20): 2123–2139
https://doi.org/10.1101/gad.267278.115 pmid: 26494788
24 Chevallier N, Corcoran C M, Lennon C, Hyjek E, Chadburn A, Bardwell V J, Licht J D, Melnick A (2004). ETO protein of t(8;21) AML is a corepressor for Bcl-6 B-cell lymphoma oncoprotein. Blood, 103(4): 1454–1463
https://doi.org/10.1182/blood-2003-06-2081 pmid: 14551142
25 Cho Y, Gorina S, Jeffrey P D, Pavletich N P (1994). Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science, 265(5170): 346–355
https://doi.org/10.1126/science.8023157 pmid: 8023157
26 Chou F S, Griesinger A, Wunderlich M, Lin S, Link K A, Shrestha M, Goyama S, Mizukawa B, Shen S, Marcucci G, Mulloy J C (2012). The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO. Blood, 120(4): 709–719
https://doi.org/10.1182/blood-2012-01-403212 pmid: 22337712
27 Chou F S, Wunderlich M, Griesinger A, Mulloy J C (2011). N-Ras(G12D) induces features of stepwise transformation in preleukemic human umbilical cord blood cultures expressing the AML1-ETO fusion gene. Blood, 117(7): 2237–2240
https://doi.org/10.1182/blood-2010-01-264119 pmid: 21200020
28 Chyla B J, Moreno-Miralles I, Steapleton M A, Thompson M A, Bhaskara S, Engel M, Hiebert S W (2008). Deletion of Mtg16, a target of t(16;21), alters hematopoietic progenitor cell proliferation and lineage allocation. Mol Cell Biol, 28(20): 6234–6247
https://doi.org/10.1128/MCB.00404-08 pmid: 18710942
29 Cisse B, Caton M L, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander N S, Kant S G, Holter W, Rauch A, Zhuang Y, Reizis B (2008). Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell, 135(1): 37–48
https://doi.org/10.1016/j.cell.2008.09.016 pmid: 18854153
30 Corpora T, Roudaia L, Oo Z M, Chen W, Manuylova E, Cai X, Chen M J, Cierpicki T, Speck N A, Bushweller J H (2010). Structure of the AML1-ETO NHR3-PKA(RIIa) complex and its contribution to AML1-ETO activity. J Mol Biol, 402(3): 560–577
https://doi.org/10.1016/j.jmb.2010.08.007 pmid: 20708017
31 D’Alonzo R C, Selvamurugan N, Karsenty G, Partridge N C (2002). Physical interaction of the activator protein-1 factors c-Fos and c-Jun with Cbfa1 for collagenase-3 promoter activation. J Biol Chem, 277(1): 816–822
https://doi.org/10.1074/jbc.M107082200 pmid: 11641401
32 Davis J N, Williams B J, Herron J T, Galiano F J, Meyers S (1999). ETO-2, a new member of the ETO-family of nuclear proteins. Oncogene, 18(6): 1375–1383
https://doi.org/10.1038/sj.onc.1202412 pmid: 10022820
33 de Bruijn M F, Speck N A (2004). Core-binding factors in hematopoiesis and immune function. Oncogene, 23(24): 4238–4248
https://doi.org/10.1038/sj.onc.1207763 pmid: 15156179
34 de Guzman C G, Warren A J, Zhang Z, Gartland L, Erickson P, Drabkin H, Hiebert S W, Klug C A (2002). Hematopoietic stem cell expansion and distinct myeloid developmental abnormalities in a murine model of the AML1-ETO translocation. Mol Cell Biol, 22(15): 5506–5517
https://doi.org/10.1128/MCB.22.15.5506-5517.2002 pmid: 12101243
35 de Pooter R F, Kee B L (2010). E proteins and the regulation of early lymphocyte development. Immunol Rev, 238(1): 93–109
https://doi.org/10.1111/j.1600-065X.2010.00957.x pmid: 20969587
36 Denis C M, Langelaan D N, Kirlin A C, Chitayat S, Munro K, Spencer H L, LeBrun D P, Smith S P (2014). Functional redundancy between the transcriptional activation domains of E2A is mediated by binding to the KIX domain of CBP/p300. Nucleic Acids Res, 42(11): 7370–7382
https://doi.org/10.1093/nar/gku206 pmid: 24682819
37 Downing J R (1999). The AML1-ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance. Br J Haematol, 106(2): 296–308
https://doi.org/10.1046/j.1365-2141.1999.01377.x pmid: 10460585
38 El Omari K, Hoosdally S J, Tuladhar K, Karia D, Hall-Ponselé E, Platonova O, Vyas P, Patient R, Porcher C, Mancini E J (2013). Structural basis for LMO2-driven recruitment of the SCL:E47bHLH heterodimer to hematopoietic-specific transcriptional targets. Cell Reports, 4(1): 135–147
https://doi.org/10.1016/j.celrep.2013.06.008 pmid: 23831025
39 Elagib K E, Racke F K, Mogass M, Khetawat R, Delehanty L L, Goldfarb A N (2003). RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood, 101(11): 4333–4341
https://doi.org/10.1182/blood-2002-09-2708 pmid: 12576332
40 Engel I, Murre C (1999). Ectopic expression of E47 or E12 promotes the death of E2A-deficient lymphomas. Proc Natl Acad Sci USA, 96(3): 996–1001
https://doi.org/10.1073/pnas.96.3.996 pmid: 9927682
41 Erickson P, Gao J, Chang K S, Look T, Whisenant E, Raimondi S, Lasher R, Trujillo J, Rowley J, Drabkin H (1992). Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity to Drosophila segmentation gene, runt. Blood, 80(7): 1825–1831
pmid: 1391946
42 Erickson P F, Dessev G, Lasher R S, Philips G, Robinson M, Drabkin H A (1996). ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease. Blood, 88(5): 1813–1823
pmid: 8781439
43 Erickson P F, Robinson M, Owens G, Drabkin H A (1994). The ETO portion of acute myeloid leukemia t(8;21) fusion transcript encodes a highly evolutionarily conserved, putative transcription factor. Cancer Res, 54(7): 1782–1786
pmid: 8137293
44 Fazi F, Racanicchi S, Zardo G, Starnes L M, Mancini M, Travaglini L, Diverio D, Ammatuna E, Cimino G, Lo-Coco F, Grignani F, Nervi C (2007). Epigenetic silencing of the myelopoiesis regulator microRNA-223 by the AML1/ETO oncoprotein. Cancer Cell, 12(5): 457–466
https://doi.org/10.1016/j.ccr.2007.09.020 pmid: 17996649
45 Feinstein P G, Kornfeld K, Hogness D S, Mann R S (1995). Identification of homeotic target genes in Drosophila melanogaster including nervy, a proto-oncogene homologue. Genetics, 140(2): 573–586
pmid: 7498738
46 Fenske T S, Pengue G, Mathews V, Hanson P T, Hamm S E, Riaz N, Graubert T A (2004). Stem cell expression of the AML1/ETO fusion protein induces a myeloproliferative disorder in mice. Proc Natl Acad Sci USA, 101(42): 15184–15189
https://doi.org/10.1073/pnas.0400751101 pmid: 15477599
47 Figueroa M E, Abdel-Wahab O, Lu C, Ward P S, Patel J, Shih A, Li Y, Bhagwat N, Vasanthakumar A, Fernandez H F, Tallman M S, Sun Z, Wolniak K, Peeters J K, Liu W, Choe S E, Fantin V R, Paietta E, Löwenberg B, Licht J D, Godley L A, Delwel R, Valk P J, Thompson C B, Levine R L, Melnick A (2010). Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell, 18(6): 553–567
https://doi.org/10.1016/j.ccr.2010.11.015 pmid: 21130701
48 Fischer M A, Moreno-Miralles I, Hunt A, Chyla B J, Hiebert S W (2012). Myeloid translocation gene 16 is required for maintenance of haematopoietic stem cell quiescence. EMBO J, 31(6): 1494–1505
https://doi.org/10.1038/emboj.2011.500 pmid: 22266796
49 Fracchiolla N S, Colombo G, Finelli P, Maiolo A T, Neri A (1998). EHT, a new member of the MTG8/ETO gene family, maps on 20q11 region and is deleted in acute myeloid leukemias. Blood, 92(9): 3481–3484
pmid: 9787195
50 Frank R, Zhang J, Uchida H, Meyers S, Hiebert S W, Nimer S D (1995). The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B. Oncogene, 11(12): 2667–2674
pmid: 8545124
51 Fukuyama T, Sueoka E, Sugio Y, Otsuka T, Niho Y, Akagi K, Kozu T (2001). MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes. Oncogene, 20(43): 6225–6232
https://doi.org/10.1038/sj.onc.1204794 pmid: 11593431
52 Gamou T, Kitamura E, Hosoda F, Shimizu K, Shinohara K, Hayashi Y, Nagase T, Yokoyama Y, Ohki M (1998). The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Blood, 91(11): 4028–4037
pmid: 9596646
53 Gamsjaeger R, Liew C K, Loughlin F E, Crossley M, Mackay J P (2007). Sticky fingers: zinc-fingers as protein-recognition motifs. Trends Biochem Sci, 32(2): 63–70
https://doi.org/10.1016/j.tibs.2006.12.007 pmid: 17210253
54 Gao X N, Yan F, Lin J, Gao L, Lu X L, Wei S C, Shen N, Pang J X, Ning Q Y, Komeno Y, Deng A L, Xu Y H, Shi J L, Li Y H, Zhang D E, Nervi C, Liu S J, Yu L (2015). AML1/ETO cooperates with HIF1a to promote leukemogenesis through DNMT3a transactivation. Leukemia, 29(8): 1730–1740
https://doi.org/10.1038/leu.2015.56 pmid: 25727291
55 Gardini A, Cesaroni M, Luzi L, Okumura A J, Biggs J R, Minardi S P, Venturini E, Zhang D E, Pelicci P G, Alcalay M (2008). AML1/ETO oncoprotein is directed to AML1 binding regions and co-localizes with AML1 and HEB on its targets. PLoS Genet, 4(11): e1000275
https://doi.org/10.1371/journal.pgen.1000275 pmid: 19043539
56 Gelmetti V, Zhang J, Fanelli M, Minucci S, Pelicci P G, Lazar M A (1998). Aberrant recruitment of the nuclear receptor corepressor-histone deacetylase complex by the acute myeloid leukemia fusion partner ETO. Mol Cell Biol, 18(12): 7185–7191
https://doi.org/10.1128/MCB.18.12.7185 pmid: 9819405
57 Geng H, Brennan S, Milne T A, Chen W Y, Li Y, Hurtz C, Kweon S M, Zickl L, Shojaee S, Neuberg D, Huang C, Biswas D, Xin Y, Racevskis J, Ketterling R P, Luger S M, Lazarus H, Tallman M S, Rowe J M, Litzow M R, Guzman M L, Allis C D, Roeder R G, Müschen M, Paietta E, Elemento O, Melnick A M (2012). Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia. Cancer Discov, 2(11): 1004–1023
https://doi.org/10.1158/2159-8290.CD-12-0208 pmid: 23107779
58 Goardon N, Lambert J A, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo P H, Hoang T (2006). ETO2 coordinates cellular proliferation and differentiation during erythropoiesis. EMBO J, 25(2): 357–366
https://doi.org/10.1038/sj.emboj.7600934 pmid: 16407974
59 Goemans B F, Zwaan C M, Miller M, Zimmermann M, Harlow A, Meshinchi S, Loonen A H, Hählen K, Reinhardt D, Creutzig U, Kaspers G J, Heinrich M C (2005). Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia, 19(9): 1536–1542
https://doi.org/10.1038/sj.leu.2403870 pmid: 16015387
60 Gow C H, Guo C, Wang D, Hu Q, Zhang J (2014). Differential involvement of E2A-corepressor interactions in distinct leukemogenic pathways. Nucleic Acids Res, 42(1): 137–152
https://doi.org/10.1093/nar/gkt855 pmid: 24064250
61 Grisolano J L, O’Neal J, Cain J, Tomasson M H (2003). An activated receptor tyrosine kinase, TEL/PDGFbetaR, cooperates with AML1/ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci USA, 100(16): 9506–9511
https://doi.org/10.1073/pnas.1531730100 pmid: 12881486
62 Gross C T, McGinnis W (1996). DEAF-1, a novel protein that binds an essential region in a Deformed response element. EMBO J, 15(8): 1961–1970
pmid: 8617243
63 Gu W, Roeder R G (1997). Activation of p53 sequence-specific DNA binding by acetylation of the p53 C-terminal domain. Cell, 90(4): 595–606
https://doi.org/10.1016/S0092-8674(00)80521-8 pmid: 9288740
64 Guenther M G, Lane W S, Fischle W, Verdin E, Lazar M A, Shiekhattar R (2000). A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat protein linked to deafness. Genes Dev, 14(9): 1048–1057
pmid: 10809664
65 Guo C, Hu Q, Yan C, Zhang J (2009). Multivalent binding of the ETO corepressor to E proteins facilitates dual repression controls targeting chromatin and the basal transcription machinery. Mol Cell Biol, 29(10): 2644–2657
https://doi.org/10.1128/MCB.00073-09 pmid: 19289505
66 Hamlett I, Draper J, Strouboulis J, Iborra F, Porcher C, Vyas P (2008). Characterization of megakaryocyte GATA1-interacting proteins: the corepressor ETO2 and GATA1 interact to regulate terminal megakaryocyte maturation. Blood, 112(7): 2738–2749
https://doi.org/10.1182/blood-2008-03-146605 pmid: 18625887
67 Hartmann L, Dutta S, Opatz S, Vosberg S, Reiter K, Leubolt G, Metzeler K H, Herold T, Bamopoulos S A, Bräundl K, Zellmeier E, Ksienzyk B, Konstandin N P, Schneider S, Hopfner K P, Graf A, Krebs S, Blum H, Middeke J M, Stölzel F, Thiede C, Wolf S, Bohlander S K, Preiss C, Chen-Wichmann L, Wichmann C, Sauerland M C, Büchner T, Berdel W E, Wörmann B J, Braess J, Hiddemann W, Spiekermann K, Greif P A (2016). ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation. Nat Commun, 7: 11733
https://doi.org/10.1038/ncomms11733 pmid: 27252013
68 Hassig C A, Fleischer T C, Billin A N, Schreiber S L, Ayer D E (1997). Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell, 89(3): 341–347
https://doi.org/10.1016/S0092-8674(00)80214-7 pmid: 9150133
69 Hatlen M A, Arora K, Vacic V, Grabowska E A, Liao W, Riley-Gillis B, Oschwald D M, Wang L, Joergens J E, Shih A H, Rapaport F, Gu S, Voza F, Asai T, Neel B G, Kharas M G, Gonen M, Levine R L, Nimer S D (2016). Integrative genetic analysis of mouse and human AML identifies cooperating disease alleles. J Exp Med, 213(1): 25–34
https://doi.org/10.1084/jem.20150524 pmid: 26666262
70 Heery D M, Kalkhoven E, Hoare S, Parker M G (1997). A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature, 387(6634): 733–736
https://doi.org/10.1038/42750 pmid: 9192902
71 Heinzel T, Lavinsky R M, Mullen T M, Söderstrom M, Laherty C D, Torchia J, Yang W M, Brard G, Ngo S D, Davie J R, Seto E, Eisenman R N, Rose D W, Glass C K, Rosenfeld M G (1997). A complex containing N-CoR, mSin3 and histone deacetylase mediates transcriptional repression. Nature, 387(6628): 43–48
https://doi.org/10.1038/387043a0 pmid: 9139820
72 Hess J L, Hug B A (2004). Fusion-protein truncation provides new insights into leukemogenesis. Proc Natl Acad Sci USA, 101(49): 16985–16986
https://doi.org/10.1073/pnas.0407898101 pmid: 15572447
73 Higuchi M, O’Brien D, Kumaravelu P, Lenny N, Yeoh E J, Downing J R (2002). Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell, 1(1): 63–74
https://doi.org/10.1016/S1535-6108(02)00016-8 pmid: 12086889
74 Higueruelo A P, Jubb H, Blundell T L (2013). Protein-protein interactions as druggable targets: recent technological advances. Curr Opin Pharmacol, 13(5): 791–796
https://doi.org/10.1016/j.coph.2013.05.009 pmid: 23735579
75 Hildebrand D, Tiefenbach J, Heinzel T, Grez M, Maurer A B (2001). Multiple regions of ETO cooperate in transcriptional repression. J Biol Chem, 276(13): 9889–9895
https://doi.org/10.1074/jbc.M010582200 pmid: 11150306
76 Huang X, Peng J W, Speck N A, Bushweller J H (1999). Solution structure of core binding factor beta and map of the CBF alpha binding site. Nat Struct Biol, 6(7): 624–627
https://doi.org/10.1038/10670 pmid: 10404216
77 Hug B A, Lee S Y, Kinsler E L, Zhang J, Lazar M A (2002). Cooperative function of Aml1-ETO corepressor recruitment domains in the expansion of primary bone marrow cells. Cancer Res, 62(10): 2906–2912
pmid: 12019171
78 Hunt A, Fischer M, Engel M E, Hiebert S W (2011). Mtg16/Eto2 contributes to murine T-cell development. Mol Cell Biol, 31(13): 2544–2551
https://doi.org/10.1128/MCB.01458-10 pmid: 21536648
79 Inaba T, Roberts W M, Shapiro L H, Jolly K W, Raimondi S C, Smith S D, Look A T (1992). Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. Science, 257(5069): 531–534
https://doi.org/10.1126/science.1386162 pmid: 1386162
80 Ito Y (2004). Oncogenic potential of the RUNX gene family: ‘overview’. Oncogene, 23(24): 4198–4208
https://doi.org/10.1038/sj.onc.1207755 pmid: 15156173
81 Jakubowiak A, Pouponnot C, Berguido F, Frank R, Mao S, Massague J, Nimer S D (2000). Inhibition of the transforming growth factor beta 1 signaling pathway by the AML1/ETO leukemia-associated fusion protein. J Biol Chem, 275(51): 40282–40287
https://doi.org/10.1074/jbc.C000485200 pmid: 11032826
82 Jankovic V, Ciarrocchi A, Boccuni P, DeBlasio T, Benezra R, Nimer S D (2007). Id1 restrains myeloid commitment, maintaining the self-renewal capacity of hematopoietic stem cells. Proc Natl Acad Sci USA, 104(4): 1260–1265
https://doi.org/10.1073/pnas.0607894104 pmid: 17227850
83 Jiao B, Wu C F, Liang Y, Chen H M, Xiong S M, Chen B, Shi J Y, Wang Y Y, Wang J H, Chen Y, Li J M, Gu L J, Tang J Y, Shen Z X, Gu B W, Zhao W L, Chen Z, Chen S J (2009). AML1-ETO9a is correlated with C-KIT overexpression/mutations and indicates poor disease outcome in t(8;21) acute myeloid leukemia-M2. Leukemia, 23(9): 1598–1604
https://doi.org/10.1038/leu.2009.104 pmid: 19458628
84 Jin W, Wu K, Li Y Z, Yang W T, Zou B, Zhang F, Zhang J, Wang K K (2013). AML1-ETO targets and suppresses cathepsin G, a serine protease, which is able to degrade AML1-ETO in t(8;21) acute myeloid leukemia. Oncogene, 32(15): 1978–1987
https://doi.org/10.1038/onc.2012.204 pmid: 22641217
85 Kamps M P, Baltimore D (1993). E2A-Pbx1, the t(1;19) translocation protein of human pre-B-cell acute lymphocytic leukemia, causes acute myeloid leukemia in mice. Mol Cell Biol, 13(1): 351–357
https://doi.org/10.1128/MCB.13.1.351 pmid: 8093327
86 Kamps M P, Murre C, Sun X H, Baltimore D (1990). A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell, 60(4): 547–555
https://doi.org/10.1016/0092-8674(90)90658-2 pmid: 1967983
87 Kee B L (2009). E and ID proteins branch out. Nat Rev Immunol, 9(3): 175–184
https://doi.org/10.1038/nri2507 pmid: 19240756
88 Kim W Y, Sieweke M, Ogawa E, Wee H J, Englmeier U, Graf T, Ito Y (1999). Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. EMBO J, 18(6): 1609–1620
https://doi.org/10.1093/emboj/18.6.1609 pmid: 10075931
89 Kitabayashi I, Ida K, Morohoshi F, Yokoyama A, Mitsuhashi N, Shimizu K, Nomura N, Hayashi Y, Ohki M (1998). The AML1-MTG8 leukemic fusion protein forms a complex with a novel member of the MTG8(ETO/CDR) family, MTGR1. Mol Cell Biol, 18(2): 846–858
https://doi.org/10.1128/MCB.18.2.846 pmid: 9447981
90 Klampfer L, Zhang J, Zelenetz A O, Uchida H, Nimer S D (1996). The AML1/ETO fusion protein activates transcription of BCL-2. Proc Natl Acad Sci USA, 93(24): 14059–14064
https://doi.org/10.1073/pnas.93.24.14059 pmid: 8943060
91 Klisovic M I, Maghraby E A, Parthun M R, Guimond M, Sklenar A R, Whitman S P, Chan K K, Murphy T, Anon J, Archer K J, Rush L J, Plass C, Grever M R, Byrd J C, Marcucci G (2003). Depsipeptide (FR 901228) promotes histone acetylation, gene transcription, apoptosis and its activity is enhanced by DNA methyltransferase inhibitors in AML1/ETO-positive leukemic cells. Leukemia, 17(2): 350–358
https://doi.org/10.1038/sj.leu.2402776 pmid: 12592335
92 Komori A, Sueoka E, Fujiki H, Ishii M, Kozu T (1999). Association of MTG8 (ETO/CDR), a leukemia-related protein, with serine/threonine protein kinases and heat shock protein HSP90 in human hematopoietic cell lines. Jpn J Cancer Res, 90(1): 60–68
https://doi.org/10.1111/j.1349-7006.1999.tb00666.x pmid: 10076566
93 Krauth M T, Eder C, Alpermann T, Bacher U, Nadarajah N, Kern W, Haferlach C, Haferlach T, Schnittger S (2014). High number of additional genetic lesions in acute myeloid leukemia with t(8;21)/RUNX1-RUNX1T1: frequency and impact on clinical outcome. Leukemia, 28(7): 1449–1458
https://doi.org/10.1038/leu.2014.4 pmid: 24402164
94 Kwok C, Zeisig B B, Dong S, So C W (2010). The role of CBFbeta in AML1-ETO’s activity. Blood, 115(15): 3176–3177
https://doi.org/10.1182/blood-2009-12-260570 pmid: 20395424
95 Kwok C, Zeisig B B, Qiu J, Dong S, So C W (2009). Transforming activity of AML1-ETO is independent of CBFbeta and ETO interaction but requires formation of homo-oligomeric complexes. Proc Natl Acad Sci USA, 106(8): 2853–2858
https://doi.org/10.1073/pnas.0810558106 pmid: 19202074
96 Laherty C D, Yang W M, Sun J M, Davie J R, Seto E, Eisenman R N (1997). Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression. Cell, 89(3): 349–356
https://doi.org/10.1016/S0092-8674(00)80215-9 pmid: 9150134
97 Laraia L, McKenzie G, Spring D R, Venkitaraman A R, Huggins D J (2015). Overcoming chemical, biological, and computational challenges in the development of inhibitors targeting protein-protein interactions. Chem Biol, 22(6): 689–703
https://doi.org/10.1016/j.chembiol.2015.04.019 pmid: 26091166
98 Lenny N, Meyers S, Hiebert S W (1995). Functional domains of the t(8;21) fusion protein, AML-1/ETO. Oncogene, 11(9): 1761–1769
pmid: 7478604
99 Li F Q, Person R E, Takemaru K, Williams K, Meade-White K, Ozsahin A H, Güngör T, Moon R T, Horwitz M (2004). Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core-binding factor alpha regulation of ELA2. J Biol Chem, 279(4): 2873–2884
https://doi.org/10.1074/jbc.M310759200 pmid: 14594802
100 Li J, Wang J, Wang J, Nawaz Z, Liu J M, Qin J, Wong J (2000). Both corepressor proteins SMRT and N-CoR exist in large protein complexes containing HDAC3. EMBO J, 19(16): 4342–4350
https://doi.org/10.1093/emboj/19.16.4342 pmid: 10944117
101 Li L M, Chen Z X, Cen J N, Shen H J, Yao L, Wang Y Y, Qi X F (2012). Monitoring the expression ratio of AML1-ETO9a isoform in t(8;21) acute myeloid leukemia and its significance. Zhonghua Xue Ye Xue Za Zhi, 33(1): 1–5
pmid: 22575183
102 Li Q L, Ito K, Sakakura C, Fukamachi H, Inoue K, Chi X Z, Lee K Y, Nomura S, Lee C W, Han S B, Kim H M, Kim W J, Yamamoto H, Yamashita N, Yano T, Ikeda T, Itohara S, Inazawa J, Abe T, Hagiwara A, Yamagishi H, Ooe A, Kaneda A, Sugimura T, Ushijima T, Bae S C, Ito Y (2002). Causal relationship between the loss of RUNX3 expression and gastric cancer. Cell, 109(1): 113–124
https://doi.org/10.1016/S0092-8674(02)00690-6 pmid: 11955451
103 Li Y, Gao L, Luo X, Wang L, Gao X, Wang W, Sun J, Dou L, Li J, Xu C, Wang L, Zhou M, Jiang M, Zhou J, Caligiuri M A, Nervi C, Bloomfield C D, Marcucci G, Yu L (2013). Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t(8;21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway. Blood, 121(3): 499–509
https://doi.org/10.1182/blood-2012-07-444729 pmid: 23223432
104 Li Y, Wang H, Wang X, Jin W, Tan Y, Fang H, Chen S, Chen Z, Wang K (2015a). Genome-wide studies identify a novel interplay between AML1 and AML1/ETO in t(8;21) acute myeloid leukemia. Blood, 127(2):233–242
105 Li Z, Chen P, Su R, Li Y, Hu C, Wang Y, Arnovitz S, He M, Gurbuxani S, Zuo Z, Elkahloun A G, Li S, Weng H, Huang H, Neilly M B, Wang S, Olson E N, Larson R A, Le Beau M M, Zhang J, Jiang X, Wei M, Jin J, Liu P P, Chen J (2015b). Overexpression and knockout of miR-126 both promote leukemogenesis. Blood, 126(17): 2005–2015
https://doi.org/10.1182/blood-2015-04-639062 pmid: 26361793
106 Li Z, Lu J, Sun M, Mi S, Zhang H, Luo R T, Chen P, Wang Y, Yan M, Qian Z, Neilly M B, Jin J, Zhang Y, Bohlander S K, Zhang D E, Larson R A, Le Beau M M, Thirman M J, Golub T R, Rowley J D, Chen J (2008). Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci USA, 105(40): 15535–15540
https://doi.org/10.1073/pnas.0808266105 pmid: 18832181
107 Libermann T A, Pan Z, Akbarali Y, Hetherington C J, Boltax J, Yergeau D A, Zhang D E (1999). AML1 (CBFalpha2) cooperates with B cell-specific activating protein (BSAP/PAX5) in activation of the B cell-specific BLK gene promoter. J Biol Chem, 274(35): 24671–24676
https://doi.org/10.1074/jbc.274.35.24671 pmid: 10455134
108 Licciulli S, Cambiaghi V, Scafetta G, Gruszka A M, Alcalay M (2010). Pirin downregulation is a feature of AML and leads to impairment of terminal myeloid differentiation. Leukemia, 24(2): 429–437
https://doi.org/10.1038/leu.2009.247 pmid: 20010624
109 Linggi B, Müller-Tidow C, van de Locht L, Hu M, Nip J, Serve H, Berdel W E, van der Reijden B, Quelle D E, Rowley J D, Cleveland J, Jansen J H, Pandolfi P P, Hiebert S W (2002). The t(8;21) fusion protein, AML1 ETO, specifically represses the transcription of the p14(ARF) tumor suppressor in acute myeloid leukemia. Nat Med, 8(7): 743–750
https://doi.org/10.1038/nm726 pmid: 12091906
110 Liu S, Shen T, Huynh L, Klisovic M I, Rush L J, Ford J L, Yu J, Becknell B, Li Y, Liu C, Vukosavljevic T, Whitman S P, Chang K S, Byrd J C, Perrotti D, Plass C, Marcucci G (2005). Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Cancer Res, 65(4): 1277–1284
https://doi.org/10.1158/0008-5472.CAN-04-4532 pmid: 15735013
111 Liu Y, Chen W, Gaudet J, Cheney M D, Roudaia L, Cierpicki T, Klet R C, Hartman K, Laue T M, Speck N A, Bushweller J H (2007). Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO’s activity. Cancer Cell, 11(6): 483–497
https://doi.org/10.1016/j.ccr.2007.04.010 pmid: 17560331
112 Liu Y, Cheney M D, Gaudet J J, Chruszcz M, Lukasik S M, Sugiyama D, Lary J, Cole J, Dauter Z, Minor W, Speck N A, Bushweller J H (2006). The tetramer structure of the Nervy homology two domain, NHR2, is critical for AML1/ETO’s activity. Cancer Cell, 9(4): 249–260
https://doi.org/10.1016/j.ccr.2006.03.012 pmid: 16616331
113 Lo M C, Peterson L F, Yan M, Cong X, Jin F, Shia W J, Matsuura S, Ahn E Y, Komeno Y, Ly M, Ommen H B, Chen I M, Hokland P, Willman C L, Ren B, Zhang D E (2012). Combined gene expression and DNA occupancy profiling identifies potential therapeutic targets of t(8;21) AML. Blood, 120(7): 1473–1484
https://doi.org/10.1182/blood-2011-12-395335 pmid: 22740448
114 Lotem J, Levanon D, Negreanu V, Bauer O, Hantisteanu S, Dicken J, Groner Y (2015). Runx3 at the interface of immunity, inflammation and cancer. Biochim Biophys Acta, 1855(2): 131–143
pmid: 25641675
115 Lu Q, Knoepfler P S, Scheele J, Wright D D, Kamps M P (1995). Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the products of multiple murine Hox genes, some of which are themselves oncogenes. Mol Cell Biol, 15(7): 3786–3795
https://doi.org/10.1128/MCB.15.7.3786 pmid: 7791786
116 Lu Q, Wright D D, Kamps M P (1994). Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation. Mol Cell Biol, 14(6): 3938–3948
https://doi.org/10.1128/MCB.14.6.3938 pmid: 7910944
117 Lutterbach B, Sun D, Schuetz J, Hiebert S W (1998a). The MYND motif is required for repression of basal transcription from the multidrug resistance 1 promoter by the t(8;21) fusion protein. Mol Cell Biol, 18(6): 3604–3611
https://doi.org/10.1128/MCB.18.6.3604 pmid: 9584201
118 Lutterbach B, Westendorf J J, Linggi B, Patten A, Moniwa M, Davie J R, Huynh K D, Bardwell V J, Lavinsky R M, Rosenfeld M G, Glass C, Seto E, Hiebert S W (1998b). ETO, a target of t(8;21) in acute leukemia, interacts with the N-CoR and mSin3 corepressors. Mol Cell Biol, 18(12): 7176–7184
https://doi.org/10.1128/MCB.18.12.7176 pmid: 9819404
119 Mao S, Frank R C, Zhang J, Miyazaki Y, Nimer S D (1999). Functional and physical interactions between AML1 proteins and an ETS protein, MEF: implications for the pathogenesis of t(8;21)-positive leukemias. Mol Cell Biol, 19(5): 3635–3644
https://doi.org/10.1128/MCB.19.5.3635 pmid: 10207087
120 Martens J H, Mandoli A, Simmer F, Wierenga B J, Saeed S, Singh A A, Altucci L, Vellenga E, Stunnenberg H G (2012). ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia. Blood, 120(19): 4038–4048
https://doi.org/10.1182/blood-2012-05-429050 pmid: 22983443
121 Massari M E, Murre C (2000). Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol, 20(2): 429–440
https://doi.org/10.1128/MCB.20.2.429-440.2000 pmid: 10611221
122 Matheny C J, Speck M E, Cushing P R, Zhou Y, Corpora T, Regan M, Newman M, Roudaia L, Speck C L, Gu T L, Griffey S M, Bushweller J H, Speck N A (2007). Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. EMBO J, 26(4): 1163–1175
https://doi.org/10.1038/sj.emboj.7601568 pmid: 17290219
123 McGhee L, Bryan J, Elliott L, Grimes H L, Kazanjian A, Davis J N, Meyers S (2003). Gfi-1 attaches to the nuclear matrix, associates with ETO (MTG8) and histone deacetylase proteins, and represses transcription using a TSA-sensitive mechanism. J Cell Biochem, 89(5): 1005–1018
https://doi.org/10.1002/jcb.10548 pmid: 12874834
124 Meier N, Krpic S, Rodriguez P, Strouboulis J, Monti M, Krijgsveld J, Gering M, Patient R, Hostert A, Grosveld F (2006). Novel binding partners of Ldb1 are required for haematopoietic development. Development, 133(24): 4913–4923
https://doi.org/10.1242/dev.02656 pmid: 17108004
125 Mellentin J D, Murre C, Donlon T A, McCaw P S, Smith S D, Carroll A J, McDonald M E, Baltimore D, Cleary M L (1989). The gene for enhancer binding proteins E12/E47 lies at the t(1;19) breakpoint in acute leukemias. Science, 246(4928): 379–382
https://doi.org/10.1126/science.2799390 pmid: 2799390
126 Melnick A M, Westendorf J J, Polinger A, Carlile G W, Arai S, Ball H J, Lutterbach B, Hiebert S W, Licht J D (2000). The ETO protein disrupted in t(8;21)-associated acute myeloid leukemia is a corepressor for the promyelocytic leukemia zinc finger protein. Mol Cell Biol, 20(6): 2075–2086
https://doi.org/10.1128/MCB.20.6.2075-2086.2000 pmid: 10688654
127 Meyers S, Downing J R, Hiebert S W (1993). Identification of AML-1 and the (8;21) translocation protein (AML-1/ETO) as sequence-specific DNA-binding proteins: the runt homology domain is required for DNA binding and protein-protein interactions. Mol Cell Biol, 13(10): 6336–6345
https://doi.org/10.1128/MCB.13.10.6336 pmid: 8413232
128 Meyers S, Lenny N, Hiebert S W (1995). The t(8;21) fusion protein interferes with AML-1B-dependent transcriptional activation. Mol Cell Biol, 15(4): 1974–1982
https://doi.org/10.1128/MCB.15.4.1974 pmid: 7891692
129 Micol J B, Duployez N, Boissel N, Petit A, Geffroy S, Nibourel O, Lacombe C, Lapillonne H, Etancelin P, Figeac M, Renneville A, Castaigne S, Leverger G, Ifrah N, Dombret H, Preudhomme C, Abdel-Wahab O, Jourdan E (2014). Frequent ASXL2 mutations in acute myeloid leukemia patients with t(8;21)/RUNX1-RUNX1T1 chromosomal translocations. Blood, 124(9): 1445–1449
https://doi.org/10.1182/blood-2014-04-571018 pmid: 24973361
130 Minucci S, Maccarana M, Cioce M, De Luca P, Gelmetti V, Segalla S, Di Croce L, Giavara S, Matteucci C, Gobbi A, Bianchini A, Colombo E, Schiavoni I, Badaracco G, Hu X, Lazar M A, Landsberger N, Nervi C, Pelicci P G (2000). Oligomerization of RAR and AML1 transcription factors as a novel mechanism of oncogenic activation. Mol Cell, 5(5): 811–820
https://doi.org/10.1016/S1097-2765(00)80321-4 pmid: 10882117
131 Miyoshi H, Kozu T, Shimizu K, Enomoto K, Maseki N, Kaneko Y, Kamada N, Ohki M (1993). The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript. EMBO J, 12(7): 2715–2721
pmid: 8334990
132 Miyoshi H, Ohira M, Shimizu K, Mitani K, Hirai H, Imai T, Yokoyama K, Soeda E, Ohki M (1995). Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia. Nucleic Acids Res, 23(14): 2762–2769
https://doi.org/10.1093/nar/23.14.2762 pmid: 7651838
133 Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M (1991). t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proc Natl Acad Sci USA, 88(23): 10431–10434
https://doi.org/10.1073/pnas.88.23.10431 pmid: 1720541
134 Müller-Tidow C, Steffen B, Cauvet T, Tickenbrock L, Ji P, Diederichs S, Sargin B, Köhler G, Stelljes M, Puccetti E, Ruthardt M, deVos S, Hiebert S W, Koeffler H P, Berdel W E, Serve H (2004). Translocation products in acute myeloid leukemia activate the Wnt signaling pathway in hematopoietic cells. Mol Cell Biol, 24(7): 2890–2904
https://doi.org/10.1128/MCB.24.7.2890-2904.2004 pmid: 15024077
135 Mulloy J C, Cammenga J, Berguido F J, Wu K, Zhou P, Comenzo R L, Jhanwar S, Moore M A, Nimer S D (2003). Maintaining the self-renewal and differentiation potential of human CD34+ hematopoietic cells using a single genetic element. Blood, 102(13): 4369–4376
https://doi.org/10.1182/blood-2003-05-1762 pmid: 12946995
136 Mulloy J C, Cammenga J, MacKenzie K L, Berguido F J, Moore M A, Nimer S D (2002). The AML1-ETO fusion protein promotes the expansion of human hematopoietic stem cells. Blood, 99(1): 15–23
https://doi.org/10.1182/blood.V99.1.15 pmid: 11756147
137 Mulloy J C, Jankovic V, Wunderlich M, Delwel R, Cammenga J, Krejci O, Zhao H, Valk P J, Lowenberg B, Nimer S D (2005). AML1-ETO fusion protein up-regulates TRKA mRNA expression in human CD34+ cells, allowing nerve growth factor-induced expansion. Proc Natl Acad Sci USA, 102(11): 4016–4021
https://doi.org/10.1073/pnas.0404701102 pmid: 15731354
138 Nagata T, Gupta V, Sorce D, Kim W Y, Sali A, Chait B T, Shigesada K, Ito Y, Werner M H (1999). Immunoglobulin motif DNA recognition and heterodimerization of the PEBP2/CBF Runt domain. Nat Struct Biol, 6(7): 615–619
https://doi.org/10.1038/10658 pmid: 10404214
139 Nagy L, Kao H Y, Chakravarti D, Lin R J, Hassig C A, Ayer D E, Schreiber S L, Evans R M (1997). Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell, 89(3): 373–380
https://doi.org/10.1016/S0092-8674(00)80218-4 pmid: 9150137
140 Nishida S, Hosen N, Shirakata T, Kanato K, Yanagihara M, Nakatsuka S, Hoshida Y, Nakazawa T, Harada Y, Tatsumi N, Tsuboi A, Kawakami M, Oka Y, Oji Y, Aozasa K, Kawase I, Sugiyama H (2006). AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1. Blood, 107(8): 3303–3312
https://doi.org/10.1182/blood-2005-04-1656 pmid: 16380455
141 Nourse J, Mellentin J D, Galili N, Wilkinson J, Stanbridge E, Smith S D, Cleary M L (1990). Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell, 60(4): 535–545
https://doi.org/10.1016/0092-8674(90)90657-Z pmid: 1967982
142 Ogawa E, Inuzuka M, Maruyama M, Satake M, Naito-Fujimoto M, Ito Y, Shigesada K (1993). Molecular cloning and characterization of PEBP2 beta, the heterodimeric partner of a novel Drosophila runt-related DNA binding protein PEBP2 alpha. Virology, 194(1): 314–331
https://doi.org/10.1006/viro.1993.1262 pmid: 8386878
143 Okuda T, Cai Z, Yang S, Lenny N, Lyu C J, van Deursen J M, Harada H, Downing J R (1998). Expression of a knocked-in AML1-ETO leukemia gene inhibits the establishment of normal definitive hematopoiesis and directly generates dysplastic hematopoietic progenitors. Blood, 91(9): 3134–3143
pmid: 9558367
144 Okuda T, van Deursen J, Hiebert S W, Grosveld G, Downing J R (1996). AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell, 84(2): 321–330
https://doi.org/10.1016/S0092-8674(00)80986-1 pmid: 8565077
145 Okumura A J, Peterson L F, Okumura F, Boyapati A, Zhang D E (2008). t(8;21)(q22;q22) Fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression. Blood, 112(4): 1392–1401
https://doi.org/10.1182/blood-2007-11-124735 pmid: 18511808
146 Pabst T, Mueller B U, Harakawa N, Schoch C, Haferlach T, Behre G, Hiddemann W, Zhang D E, Tenen D G (2001). AML1-ETO downregulates the granulocytic differentiation factor C/EBPalpha in t(8;21) myeloid leukemia. Nat Med, 7(4): 444–451
https://doi.org/10.1038/86515 pmid: 11283671
147 Park S, Chen W, Cierpicki T, Tonelli M, Cai X, Speck N A, Bushweller J H (2009a). Structure of the AML1-ETO eTAFH domain-HEB peptide complex and its contribution to AML1-ETO activity. Blood, 113(15): 3558–3567
https://doi.org/10.1182/blood-2008-06-161307 pmid: 19204326
148 Park S, Speck N A, Bushweller J H (2009b). The role of CBFbeta in AML1-ETO’s activity. Blood, 114(13): 2849–2850
https://doi.org/10.1182/blood-2009-07-231233 pmid: 19779050
149 Park S T, Nolan G P, Sun X H (1999). Growth inhibition and apoptosis due to restoration of E2A activity in T cell acute lymphoblastic leukemia cells. J Exp Med, 189(3): 501–508
https://doi.org/10.1084/jem.189.3.501 pmid: 9927512
150 Peterson L F, Yan M, Zhang D E (2007). The p21Waf1 pathway is involved in blocking leukemogenesis by the t(8;21) fusion protein AML1-ETO. Blood, 109(10): 4392–4398
https://doi.org/10.1182/blood-2006-03-012575 pmid: 17284535
151 Peterson L F, Zhang D E (2004). The 8;21 translocation in leukemogenesis. Oncogene, 23(24): 4255–4262
https://doi.org/10.1038/sj.onc.1207727 pmid: 15156181
152 Petrovick M S, Hiebert S W, Friedman A D, Hetherington C J, Tenen D G, Zhang D E (1998). Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different regions of AML1. Mol Cell Biol, 18(7): 3915–3925
https://doi.org/10.1128/MCB.18.7.3915 pmid: 9632776
153 Plevin M J, Zhang J, Guo C, Roeder R G, Ikura M (2006). The acute myeloid leukemia fusion protein AML1-ETO targets E proteins via a paired amphipathic helix-like TBP-associated factor homology domain. Proc Natl Acad Sci USA, 103(27): 10242–10247
https://doi.org/10.1073/pnas.0603463103 pmid: 16803958
154 Ptasinska A, Assi S A, Mannari D, James S R, Williamson D, Dunne J, Hoogenkamp M, Wu M, Care M, McNeill H, Cauchy P, Cullen M, Tooze R M, Tenen D G, Young B D, Cockerill P N, Westhead D R, Heidenreich O, Bonifer C (2012). Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia, 26(8): 1829–1841
https://doi.org/10.1038/leu.2012.49 pmid: 22343733
155 Ptasinska A, Assi S A, Martinez-Soria N, Imperato M R, Piper J, Cauchy P, Pickin A, James S R, Hoogenkamp M, Williamson D, Wu M, Tenen D G, Ott S, Westhead D R, Cockerill P N, Heidenreich O, Bonifer C (2014). Identification of a dynamic core transcriptional network in t(8;21) AML that regulates differentiation block and self-renewal. Cell Reports, 8(6): 1974–1988
https://doi.org/10.1016/j.celrep.2014.08.024 pmid: 25242324
156 Quong M W, Romanow W J, Murre C (2002). E protein function in lymphocyte development. Annu Rev Immunol, 20(1): 301–322
https://doi.org/10.1146/annurev.immunol.20.092501.162048 pmid: 11861605
157 Rampal R, Alkalin A, Madzo J, Vasanthakumar A, Pronier E, Patel J, Li Y, Ahn J, Abdel-Wahab O, Shih A, Lu C, Ward P S, Tsai J J, Hricik T, Tosello V, Tallman J E, Zhao X, Daniels D, Dai Q, Ciminio L, Aifantis I, He C, Fuks F, Tallman M S, Ferrando A, Nimer S, Paietta E, Thompson C B, Licht J D, Mason C E, Godley L A, Melnick A, Figueroa M E, Levine R L (2014). DNA hydroxymethylation profiling reveals that WT1 mutations result in loss of TET2 function in acute myeloid leukemia. Cell Reports, 9(5): 1841–1855
https://doi.org/10.1016/j.celrep.2014.11.004 pmid: 25482556
158 Rasmussen K D, Jia G, Johansen J V, Pedersen M T, Rapin N, Bagger F O, Porse B T, Bernard O A, Christensen J, Helin K (2015). Loss of TET2 in hematopoietic cells leads to DNA hypermethylation of active enhancers and induction of leukemogenesis. Genes Dev, 29(9): 910–922
https://doi.org/10.1101/gad.260174.115 pmid: 25886910
159 Reikvam H, Hatfield K J, Kittang A O, Hovland R, Bruserud Ø (2011). Acute myeloid leukemia with the t(8;21) translocation: clinical consequences and biological implications. J Biomed Biotechnol, 2011: 104631
https://doi.org/10.1155/2011/104631 pmid: 21629739
160 Rhoades K L, Hetherington C J, Harakawa N, Yergeau D A, Zhou L, Liu L Q, Little M T, Tenen D G, Zhang D E (2000). Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model. Blood, 96(6): 2108–2115
pmid: 10979955
161 Rhoades K L, Hetherington C J, Rowley J D, Hiebert S W, Nucifora G, Tenen D G, Zhang D E (1996). Synergistic up-regulation of the myeloid-specific promoter for the macrophage colony-stimulating factor receptor by AML1 and the t(8;21) fusion protein may contribute to leukemogenesis. Proc Natl Acad Sci USA, 93(21): 11895–11900
https://doi.org/10.1073/pnas.93.21.11895 pmid: 8876234
162 Rolland T, Taşan M, Charloteaux B, Pevzner S J, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R, Kamburov A, Ghiassian S D, Yang X, Ghamsari L, Balcha D, Begg B E, Braun P, Brehme M, Broly M P, Carvunis A R, Convery-Zupan D, Corominas R, Coulombe-Huntington J, Dann E, Dreze M, Dricot A, Fan C, Franzosa E, Gebreab F, Gutierrez B J, Hardy M F, Jin M, Kang S, Kiros R, Lin G N, Luck K, MacWilliams A, Menche J, Murray R R, Palagi A, Poulin M M, Rambout X, Rasla J, Reichert P, Romero V, Ruyssinck E, Sahalie J M, Scholz A, Shah A A, Sharma A, Shen Y, Spirohn K, Tam S, Tejeda A O, Trigg S A, Twizere J C, Vega K, Walsh J, Cusick M E, Xia Y, Barabási A L, Iakoucheva L M, Aloy P, De Las Rivas J, Tavernier J, Calderwood M A, Hill D E, Hao T, Roth F P, Vidal M (2014). A proteome-scale map of the human interactome network. Cell, 159(5): 1212–1226
https://doi.org/10.1016/j.cell.2014.10.050 pmid: 25416956
163 Ross M E, Mahfouz R, Onciu M, Liu H C, Zhou X, Song G, Shurtleff S A, Pounds S, Cheng C, Ma J, Ribeiro R C, Rubnitz J E, Girtman K, Williams W K, Raimondi S C, Liang D C, Shih L Y, Pui C H, Downing J R (2004). Gene expression profiling of pediatric acute myelogenous leukemia. Blood, 104(12): 3679–3687
https://doi.org/10.1182/blood-2004-03-1154 pmid: 15226186
164 Roudaia L, Cheney M D, Manuylova E, Chen W, Morrow M, Park S, Lee C T, Kaur P, Williams O, Bushweller J H, Speck N A (2009). CBFbeta is critical for AML1-ETO and TEL-AML1 activity. Blood, 113(13): 3070–3079
https://doi.org/10.1182/blood-2008-03-147207 pmid: 19179469
165 Rowley J D (1973). Identificaton of a translocation with quinacrine fluorescence in a patient with acute leukemia. Ann Genet, 16(2): 109–112
pmid: 4125056
166 Rowley J D (1999). The role of chromosome translocations in leukemogenesis. Semin Hematol, 36(4 Suppl 7): 59–72
pmid: 10595755
167 Rual J F, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz G F, Gibbons F D, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg D S, Zhang L V, Wong S L, Franklin G, Li S, Albala J S, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski R S, Vandenhaute J, Zoghbi H Y, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick M E, Hill D E, Roth F P, Vidal M (2005). Towards a proteome-scale map of the human protein-protein interaction network. Nature, 437(7062): 1173–1178
https://doi.org/10.1038/nature04209 pmid: 16189514
168 Salat D, Liefke R, Wiedenmann J, Borggrefe T, Oswald F (2008). ETO, but not leukemogenic fusion protein AML1/ETO, augments RBP-Jkappa/SHARP-mediated repression of notch target genes. Mol Cell Biol, 28(10): 3502–3512
https://doi.org/10.1128/MCB.01966-07 pmid: 18332109
169 Samuel A Stoner R D, Lo M C, Zhang D E (2013). Tumor Suppressor RASSF2 Is Downregulated By The RUNX1-ETO Fusion Protein In t(8;21)+ Acute Myeloid Leukemia. Blood, 122: 1268
170 Schessl C, Rawat V P, Cusan M, Deshpande A, Kohl T M, Rosten P M, Spiekermann K, Humphries R K, Schnittger S, Kern W, Hiddemann W, Quintanilla-Martinez L, Bohlander S K, Feuring-Buske M, Buske C (2005). The AML1-ETO fusion gene and the FLT3 length mutation collaborate in inducing acute leukemia in mice. J Clin Invest, 115(8): 2159–2168
https://doi.org/10.1172/JCI24225 pmid: 16025155
171 Scholl C, Gilliland D G, Fröhling S (2008). Deregulation of signaling pathways in acute myeloid leukemia. Semin Oncol, 35(4): 336–345
https://doi.org/10.1053/j.seminoncol.2008.04.004 pmid: 18692684
172 Schuh A H, Tipping A J, Clark A J, Hamlett I, Guyot B, Iborra F J, Rodriguez P, Strouboulis J, Enver T, Vyas P, Porcher C (2005). ETO-2 associates with SCL in erythroid cells and megakaryocytes and provides repressor functions in erythropoiesis. Mol Cell Biol, 25(23): 10235–10250
https://doi.org/10.1128/MCB.25.23.10235-10250.2005 pmid: 16287841
173 Schwartz R, Engel I, Fallahi-Sichani M, Petrie H T, Murre C (2006). Gene expression patterns define novel roles for E47 in cell cycle progression, cytokine-mediated signaling, and T lineage development. Proc Natl Acad Sci USA, 103(26): 9976–9981
https://doi.org/10.1073/pnas.0603728103 pmid: 16782810
174 Seita J, Weissman I L (2010). Hematopoietic stem cell: self-renewal versus differentiation. Wiley Interdiscip Rev Syst Biol Med, 2(6): 640–653
https://doi.org/10.1002/wsbm.86 pmid: 20890962
175 Shen Y, Zhu Y M, Fan X, Shi J Y, Wang Q R, Yan X J, Gu Z H, Wang Y Y, Chen B, Jiang C L, Yan H, Chen F F, Chen H M, Chen Z, Jin J, Chen S J (2011). Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood, 118(20): 5593–5603
https://doi.org/10.1182/blood-2011-03-343988 pmid: 21881046
176 Shia W J, Okumura A J, Yan M, Sarkeshik A, Lo M C, Matsuura S, Komeno Y, Zhao X, Nimer S D, Yates J R 3rd, Zhang D E (2012). PRMT1 interacts with AML1-ETO to promote its transcriptional activation and progenitor cell proliferative potential. Blood, 119(21): 4953–4962
https://doi.org/10.1182/blood-2011-04-347476 pmid: 22498736
177 Shiina M, Hamada K, Inoue-Bungo T, Shimamura M, Uchiyama A, Baba S, Sato K, Yamamoto M, Ogata K (2015). A novel allosteric mechanism on protein-DNA interactions underlying the phosphorylation-dependent regulation of Ets1 target gene expressions. J Mol Biol, 427(8): 1655–1669
https://doi.org/10.1016/j.jmb.2014.07.020 pmid: 25083921
178 Shrivastava T, Mino K, Babayeva N D, Baranovskaya O I, Rizzino A, Tahirov T H (2014). Structural basis of Ets1 activation by Runx1. Leukemia, 28(10): 2040–2048
https://doi.org/10.1038/leu.2014.111 pmid: 24646888
179 Sun X J, Wang Z, Wang L, Jiang Y, Kost N, Soong T D, Chen W Y, Tang Z, Nakadai T, Elemento O, Fischle W, Melnick A, Patel D J, Nimer S D, Roeder R G (2013). A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature, 500(7460): 93–97
https://doi.org/10.1038/nature12287 pmid: 23812588
179a Sykes D B, Kamps M P (2001). Estrogen-dependent E2a/Pbx1 myeloid cell Lines exhibit conditional differentiation that can be arrested by other leukemic oncoproteins. Blood, 98: 2308–2318
180 Tahirov T H, Inoue-Bungo T, Morii H, Fujikawa A, Sasaki M, Kimura K, Shiina M, Sato K, Kumasaka T, Yamamoto M, Ishii S, Ogata K (2001). Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta. Cell, 104(5): 755–767
https://doi.org/10.1016/S0092-8674(01)00271-9 pmid: 11257229
181 Tanaka T, Tanaka K, Ogawa S, Kurokawa M, Mitani K, Nishida J, Shibata Y, Yazaki Y, Hirai H (1995). An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms. EMBO J, 14(2): 341–350
pmid: 7530657
182 Tang Y, Zhao W, Chen Y, Zhao Y, Gu W (2008). Acetylation is indispensable for p53 activation. Cell, 133(4): 612–626
https://doi.org/10.1016/j.cell.2008.03.025 pmid: 18485870
183 Tonks A, Pearn L, Musson M, Gilkes A, Mills K I, Burnett A K, Darley R L (2007). Transcriptional dysregulation mediated by RUNX1-RUNX1T1 in normal human progenitor cells and in acute myeloid leukaemia. Leukemia, 21(12): 2495–2505
https://doi.org/10.1038/sj.leu.2404961 pmid: 17898786
184 Toyonaga K, Kikuchi H, Yamashita K, Nakayama M, Chijiiwa K, Nakayama T (2009). E2A participates in a fine control of pre-mature B-cell apoptosis mediated by B-cell receptor signaling via transcriptional regulation of survivin, IAP2 and caspase-8 genes. FEBS J, 276(5): 1418–1428
https://doi.org/10.1111/j.1742-4658.2009.06881.x pmid: 19187225
185 Trombly D J, Whitfield T W, Padmanabhan S, Gordon J A, Lian J B, van Wijnen A J, Zaidi S K, Stein J L, Stein G S (2015). Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells. BMC Genomics, 16(1): 309
https://doi.org/10.1186/s12864-015-1445-0 pmid: 25928846
186 Valk P J, Verhaak R G, Beijen M A, Erpelinck C A, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer J M, Beverloo H B, Moorhouse M J, van der Spek P J, Löwenberg B, Delwel R (2004). Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med, 350(16): 1617–1628
https://doi.org/10.1056/NEJMoa040465 pmid: 15084694
187 Wang J, Hoshino T, Redner R L, Kajigaya S, Liu J M (1998). ETO, fusion partner in t(8;21) acute myeloid leukemia, represses transcription by interaction with the human N-CoR/mSin3/HDAC1 complex. Proc Natl Acad Sci USA, 95(18): 10860–10865
https://doi.org/10.1073/pnas.95.18.10860 pmid: 9724795
188 Wang L, Gural A, Sun X J, Zhao X, Perna F, Huang G, Hatlen M A, Vu L, Liu F, Xu H, Asai T, Xu H, Deblasio T, Menendez S, Voza F, Jiang Y, Cole P A, Zhang J, Melnick A, Roeder R G, Nimer S D (2011a). The leukemogenicity of AML1-ETO is dependent on site-specific lysine acetylation. Science, 333(6043): 765–769
https://doi.org/10.1126/science.1201662 pmid: 21764752
189 Wang L, Man N, Sun X J, Tan Y, Cao M G, Liu F, Hatlen M, Xu H, Huang G, Mattlin M, Mehta A, Rampersaud E, Benezra R, Nimer S D (2015). Regulation of AKT signaling by Id1 controls t(8;21) leukemia initiation and progression. Blood, 126(5): 640–650
https://doi.org/10.1182/blood-2015-03-635532 pmid: 26084673
190 Wang X, Truckses D M, Takada S, Matsumura T, Tanese N, Jacobson R H (2007). Conserved region I of human coactivator TAF4 binds to a short hydrophobic motif present in transcriptional regulators. Proc Natl Acad Sci USA, 104(19): 7839–7844
https://doi.org/10.1073/pnas.0608570104 pmid: 17483474
191 Wang Y Y, Zhao L J, Wu C F, Liu P, Shi L, Liang Y, Xiong S M, Mi J Q, Chen Z, Ren R, Chen S J (2011b). C-KIT mutation cooperates with full-length AML1-ETO to induce acute myeloid leukemia in mice. Proc Natl Acad Sci USA, 108(6): 2450–2455
https://doi.org/10.1073/pnas.1019625108 pmid: 21262832
192 Warren A J, Bravo J, Williams R L, Rabbitts T H (2000). Structural basis for the heterodimeric interaction between the acute leukaemia-associated transcription factors AML1 and CBFbeta. EMBO J, 19(12): 3004–3015
https://doi.org/10.1093/emboj/19.12.3004 pmid: 10856244
193 Wei H, Liu X, Xiong X, Wang Y, Rao Q, Wang M, Wang J (2008). AML1-ETO interacts with Sp1 and antagonizes Sp1 transactivity through RUNT domain. FEBS Lett, 582(15): 2167–2172
https://doi.org/10.1016/j.febslet.2008.05.030 pmid: 18519037
194 Wei Y, Liu S, Lausen J, Woodrell C, Cho S, Biris N, Kobayashi N, Wei Y, Yokoyama S, Werner M H (2007). A TAF4-homology domain from the corepressor ETO is a docking platform for positive and negative regulators of transcription. Nat Struct Mol Biol, 14(7): 653–661
https://doi.org/10.1038/nsmb1258 pmid: 17572682
195 Westendorf J J, Yamamoto C M, Lenny N, Downing J R, Selsted M E, Hiebert S W (1998). The t(8;21) fusion product, AML-1-ETO, associates with C/EBP-alpha, inhibits C/EBP-alpha-dependent transcription, and blocks granulocytic differentiation. Mol Cell Biol, 18(1): 322–333
https://doi.org/10.1128/MCB.18.1.322 pmid: 9418879
196 Wildonger J, Mann R S (2005). The t(8;21) translocation converts AML1 into a constitutive transcriptional repressor. Development, 132(10): 2263–2272
https://doi.org/10.1242/dev.01824 pmid: 15829516
197 Wolford J K, Prochazka M (1998). Structure and expression of the human MTG8/ETO gene. Gene, 212(1): 103–109
https://doi.org/10.1016/S0378-1119(98)00141-3 pmid: 9661669
198 Wood J D, Nucifora F C Jr, Duan K, Zhang C, Wang J, Kim Y, Schilling G, Sacchi N, Liu J M, Ross C A (2000). Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription. J Cell Biol, 150(5): 939–948
https://doi.org/10.1083/jcb.150.5.939 pmid: 10973986
199 Yamaguchi Y, Kurokawa M, Imai Y, Izutsu K, Asai T, Ichikawa M, Yamamoto G, Nitta E, Yamagata T, Sasaki K, Mitani K, Ogawa S, Chiba S, Hirai H (2004). AML1 is functionally regulated through p300-mediated acetylation on specific lysine residues. J Biol Chem, 279(15): 15630–15638
https://doi.org/10.1074/jbc.M400355200 pmid: 14752096
200 Yan M, Ahn E Y, Hiebert S W, Zhang D E (2009). RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis. Blood, 113(4): 883–886
https://doi.org/10.1182/blood-2008-04-153742 pmid: 19036704
201 Yan M, Burel S A, Peterson L F, Kanbe E, Iwasaki H, Boyapati A, Hines R, Akashi K, Zhang D E (2004). Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development. Proc Natl Acad Sci USA, 101(49): 17186–17191
https://doi.org/10.1073/pnas.0406702101 pmid: 15569932
202 Yan M, Kanbe E, Peterson L F, Boyapati A, Miao Y, Wang Y, Chen I M, Chen Z, Rowley J D, Willman C L, Zhang D E (2006). A previously unidentified alternatively spliced isoform of t(8;21) transcript promotes leukemogenesis. Nat Med, 12(8): 945–949
https://doi.org/10.1038/nm1443 pmid: 16892037
203 Yan W, Young A Z, Soares V C, Kelley R, Benezra R, Zhuang Y (1997). High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice. Mol Cell Biol, 17(12): 7317–7327
https://doi.org/10.1128/MCB.17.12.7317 pmid: 9372963
204 Yang G, Khalaf W, van de Locht L, Jansen J H, Gao M, Thompson M A, van der Reijden B A, Gutmann D H, Delwel R, Clapp D W, Hiebert S W (2005). Transcriptional repression of the Neurofibromatosis-1 tumor suppressor by the t(8;21) fusion protein. Mol Cell Biol, 25(14): 5869–5879
https://doi.org/10.1128/MCB.25.14.5869-5879.2005 pmid: 15988004
205 Yergeau D A, Hetherington C J, Wang Q, Zhang P, Sharpe A H, Binder M, Marín-Padilla M, Tenen D G, Speck N A, Zhang D E (1997). Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nat Genet, 15(3): 303–306
https://doi.org/10.1038/ng0397-303 pmid: 9054947
206 Yohe S (2015). Molecular genetic markers in acute myeloid leukemia. J Clin Med, 4(3): 460–478
https://doi.org/10.3390/jcm4030460 pmid: 26239249
207 Yuan Y, Zhou L, Miyamoto T, Iwasaki H, Harakawa N, Hetherington C J, Burel S A, Lagasse E, Weissman I L, Akashi K, Zhang D E (2001). AML1-ETO expression is directly involved in the development of acute myeloid leukemia in the presence of additional mutations. Proc Natl Acad Sci USA, 98(18): 10398–10403
https://doi.org/10.1073/pnas.171321298 pmid: 11526243
208 Zamir I, Zhang J, Lazar M A (1997). Stoichiometric and steric principles governing repression by nuclear hormone receptors. Genes Dev, 11(7): 835–846
https://doi.org/10.1101/gad.11.7.835 pmid: 9106656
209 Zhang D E, Hetherington C J, Meyers S, Rhoades K L, Larson C J, Chen H M, Hiebert S W, Tenen D G (1996). CCAAT enhancer-binding protein (C/EBP) and AML1 (CBF alpha2) synergistically activate the macrophage colony-stimulating factor receptor promoter. Mol Cell Biol, 16(3): 1231–1240
https://doi.org/10.1128/MCB.16.3.1231 pmid: 8622667
210 Zhang J, Hug B A, Huang E Y, Chen C W, Gelmetti V, Maccarana M, Minucci S, Pelicci P G, Lazar M A (2001). Oligomerization of ETO is obligatory for corepressor interaction. Mol Cell Biol, 21(1): 156–163
https://doi.org/10.1128/MCB.21.1.156-163.2001 pmid: 11113190
211 Zhang J, Kalkum M, Chait B T, Roeder R G (2002). The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK pathway through the integral subunit GPS2. Mol Cell, 9(3): 611–623
https://doi.org/10.1016/S1097-2765(02)00468-9 pmid: 11931768
212 Zhang J, Kalkum M, Yamamura S, Chait B T, Roeder R G (2004). E protein silencing by the leukemogenic AML1-ETO fusion protein. Science, 305(5688): 1286–1289
https://doi.org/10.1126/science.1097937 pmid: 15333839
213 Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D (1997). Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex. Cell, 89(3): 357–364
https://doi.org/10.1016/S0092-8674(00)80216-0 pmid: 9150135
214 Zhang Y W, Yasui N, Ito K, Huang G, Fujii M, Hanai J, Nogami H, Ochi T, Miyazono K, Ito Y (2000). A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci USA, 97(19): 10549–10554
https://doi.org/10.1073/pnas.180309597 pmid: 10962029
215 Zhao F, Vilardi A, Neely R J, Choi J K (2001). Promotion of cell cycle progression by basic helix-loop-helix E2A. Mol Cell Biol, 21(18): 6346–6357
https://doi.org/10.1128/MCB.21.18.6346-6357.2001 pmid: 11509675
216 Zheng X, Beissert T, Kukoc-Zivojnov N, Puccetti E, Altschmied J, Strolz C, Boehrer S, Gul H, Schneider O, Ottmann O G, Hoelzer D, Henschler R, Ruthardt M (2004). Gamma-catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells. Blood, 103(9): 3535–3543
https://doi.org/10.1182/blood-2003-09-3335 pmid: 14739224
217 Zuber J, Radtke I, Pardee T S, Zhao Z, Rappaport A R, Luo W, McCurrach M E, Yang M M, Dolan M E, Kogan S C, Downing J R, Lowe S W (2009). Mouse models of human AML accurately predict chemotherapy response. Genes Dev, 23(7): 877–889
https://doi.org/10.1101/gad.1771409 pmid: 19339691
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