Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

doi:10.1007/s11684-021-0877-y

Frontiers of Medicine

2022, Vol. 16

Issue (3): 442-458 https://doi.org/10.1007/s11684-021-0877-y

本期目录

Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia

Mengping Xi^1,², Shanshan Guo^1,², Caicike Bayin^1,², Lijun peng^1,², Florent Chuffart^2,³, Ekaterina Bourova-Flin^2,³, Sophie Rousseaux^2,³(

), Saadi Khochbin^2,³(

), Jian-Qing Mi^1,²(

), Jin Wang^1,²(

)

¹. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
². Pôle de Recherches Sino-Français en Science du Vivant et Génomique, Shanghai 200025, China
³. CNRS UMR 5309/INSERM U1209/Université Grenoble Alpes/Institute for Advanced Biosciences, 38706 La Tronche, France

全文: PDF(2292 KB) HTML

Abstract：

T-cell acute lymphoblastic leukemia (T-ALL) is one of the most dangerous hematological malignancies, with high tumor heterogeneity and poor prognosis. More than 60% of T-ALL patients carry NOTCH1 gene mutations, leading to abnormal expression of downstream target genes and aberrant activation of various signaling pathways. We found that chidamide, an HDAC inhibitor, exerts an antitumor effect on T-ALL cell lines and primary cells including an anti-NOTCH1 activity. In particular, chidamide inhibits the NOTCH1-MYC signaling axis by down-regulating the level of the intracellular form of NOTCH1 (NICD1) as well as MYC, partly through their ubiquitination and degradation by the proteasome pathway. We also report here the preliminary results of our clinical trial supporting that a treatment by chidamide reduces minimal residual disease (MRD) in patients and is well tolerated. Our results highlight the effectiveness and safety of chidamide in the treatment of T-ALL patients, including those with NOTCH1 mutations and open the way to a new therapeutic strategy for these patients.

Key words： T-cell acute lymphoblastic leukemia HDAC inhibitor chidamide NOTCH1 MYC ubiquitination

收稿日期: 2021-03-11 出版日期: 2022-07-18

Corresponding Author(s): Sophie Rousseaux,Saadi Khochbin,Jian-Qing Mi,Jin Wang

引用本文:

. [J]. Frontiers of Medicine, 2022, 16(3): 442-458.
Mengping Xi, Shanshan Guo, Caicike Bayin, Lijun peng, Florent Chuffart, Ekaterina Bourova-Flin, Sophie Rousseaux, Saadi Khochbin, Jian-Qing Mi, Jin Wang. Chidamide inhibits the NOTCH1-MYC signaling axis in T-cell acute lymphoblastic leukemia. Front. Med., 2022, 16(3): 442-458.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-021-0877-y
https://academic.hep.com.cn/fmd/CN/Y2022/V16/I3/442

Fig.1

Fig.2

Fig.3

Fig.4

Fig.5

Fig.6

Fig.7

1	JC Alvarnas, PA Brown, P Aoun, KK Ballen, SK Barta, U Borate, MW Boyer, PW Burke, R Cassaday, JE Castro, PF Coccia, SE Coutre, LE Damon, DJ DeAngelo, D Douer, O Frankfurt, JP Greer, RA Johnson, HM Kantarjian, RB Klisovic, G Kupfer, M Litzow, A Liu, AV Rao, B Shah, GL Uy, ES Wang, AD Zelenetz, K Gregory, C Smith. Acute Lymphoblastic Leukemia, Version 2.2015. J Natl Compr Canc Netw 2015; 13(10): 1240–1279 https://doi.org/10.6004/jnccn.2015.0153 pmid: 26483064
2	SP Hunger, CG Mullighan. Acute lymphoblastic leukemia in children. N Engl J Med 2015; 373(16): 1541–1552 https://doi.org/10.1056/NEJMra1400972 pmid: 26465987
3	S Aref, M El Agdar, O Salama, TA Zeid, M Sabry. Significance of NOTCH1 mutations détections in T-acute lymphoblastic leukemia patients. Cancer Biomark 2020; 27(2): 157–162 https://doi.org/10.3233/CBM-190967 pmid: 31796666
4	GS Guru Murthy, SK Pondaiah, S Abedin, E Atallah. Incidence and survival of T-cell acute lymphoblastic leukemia in the United States. Leuk Lymphoma 2019; 60(5): 1171–1178 pmid: 30407885
5	I Aldoss, AS Stein. Advances in adult acute lymphoblastic leukemia therapy. Leuk Lymphoma 2018; 59(5): 1033–1050 https://doi.org/10.1080/10428194.2017.1354372 pmid: 28745565
6	DJ DeAngelo, D Yu, JL Johnson, SE Coutre, RM Stone, AT Stopeck, JP Gockerman, BS Mitchell, FR Appelbaum, RA Larson. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007; 109(12): 5136–5142 https://doi.org/10.1182/blood-2006-11-056754 pmid: 17344466
7	D Caracciolo, C Riillo, A Ballerini, G Gaipa, L Lhermitte, M Rossi, C Botta, E Duroyon, K Grillone, ME Gallo Cantafio, C Buracchi, G Alampi, A Gulino, B Belmonte, F Conforti, G Golino, G Juli, E Altomare, N Polerà, F Scionti, M Arbitrio, M Iannone, M Martino, P Correale, G Talarico, A Ghelli Luserna di Rorà, A Ferrari, D Concolino, S Sestito, L Pensabene, A Giordano, M Hildinger, MT Di Martino, G Martinelli, C Tripodo, V Asnafi, A Biondi, P Tagliaferri, P Tassone. Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia. J Immunother Cancer 2021; 9(2): e002026 https://doi.org/10.1136/jitc-2020-002026 pmid: 33597219
8	MJ You, LJ Medeiros, ED Hsi. T-lymphoblastic leukemia/lymphoma. Am J Clin Pathol 2015; 144(3): 411–422 https://doi.org/10.1309/AJCPMF03LVSBLHPJ pmid: 26276771
9	T Girardi, C Vicente, J Cools, K De Keersmaecker. The genetics and molecular biology of T-ALL. Blood 2017; 129(9): 1113–1123 https://doi.org/10.1182/blood-2016-10-706465 pmid: 28115373
10	Y Liu, J Easton, Y Shao, J Maciaszek, Z Wang, MR Wilkinson, K McCastlain, M Edmonson, SB Pounds, L Shi, X Zhou, X Ma, E Sioson, Y Li, M Rusch, P Gupta, D Pei, C Cheng, MA Smith, JG Auvil, DS Gerhard, MV Relling, NJ Winick, AJ Carroll, NA Heerema, E Raetz, M Devidas, CL Willman, RC Harvey, WL Carroll, KP Dunsmore, SS Winter, BL Wood, BP Sorrentino, JR Downing, ML Loh, SP Hunger, J Zhang, CG Mullighan. The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet 2017; 49(8): 1211–1218 https://doi.org/10.1038/ng.3909 pmid: 28671688
11	B Chen, L Jiang, ML Zhong, JF Li, BS Li, LJ Peng, YT Dai, BW Cui, TQ Yan, WN Zhang, XQ Weng, YY Xie, J Lu, RB Ren, SN Chen, JD Hu, DP Wu, Z Chen, JY Tang, JY Huang, JQ Mi, SJ Chen. Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2018; 115(2): 373–378 https://doi.org/10.1073/pnas.1717125115 pmid: 29279377
12	L Yuan, L Lu, Y Yang, H Sun, X Chen, Y Huang, X Wang, L Zou, L Bao. Genetic mutational profiling analysis of T cell acute lymphoblastic leukemia reveal mutant FBXW7 as a prognostic indicator for inferior survival. Ann Hematol 2015; 94(11): 1817–1828 https://doi.org/10.1007/s00277-015-2474-0 pmid: 26341754
13	CH Yeh, M Bellon, J Pancewicz-Wojtkiewicz, C Nicot. Oncogenic mutations in the FBXW7 gene of adult T-cell leukemia patients. Proc Natl Acad Sci USA 2016; 113(24): 6731–6736 https://doi.org/10.1073/pnas.1601537113 pmid: 27247421
14	M Hefazi, MR Litzow. Recent advances in the biology and treatment of T cell acute lymphoblastic leukemia. Curr Hematol Malig Rep 2018; 13(4): 265–274 https://doi.org/10.1007/s11899-018-0455-9 pmid: 29948644
15	AC McCarter, Q Wang, M Chiang. Notch in leukemia. Adv Exp Med Biol 2018; 1066: 355–394 https://doi.org/10.1007/978-3-319-89512-3_18 pmid: 30030836
16	N Takebe, D Nguyen, SX Yang. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther 2014; 141(2): 140–149 https://doi.org/10.1016/j.pharmthera.2013.09.005 pmid: 24076266
17	B Kaushik, D Pal, S Saha. Gamma secretase inhibitor: therapeutic target via NOTCH signaling in T cell acute lymphoblastic leukemia. Curr Drug Targets 2021; [Epub ahead of print] doi: 10.2174/1389450122666210203192752 https://doi.org/10.2174/1389450122666210203192752 pmid: 33538669
18	T Palomero, WK Lim, DT Odom, ML Sulis, PJ Real, A Margolin, KC Barnes, J O’Neil, D Neuberg, AP Weng, JC Aster, F Sigaux, J Soulier, AT Look, RA Young, A Califano, AA Ferrando. NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth. Proc Natl Acad Sci USA 2006; 103(48): 18261–18266 https://doi.org/10.1073/pnas.0606108103 pmid: 17114293
19	AA Margolin, T Palomero, P Sumazin, A Califano, AA Ferrando, G Stolovitzky. ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes. Proc Natl Acad Sci USA 2009; 106(1): 244–249 https://doi.org/10.1073/pnas.0806445106 pmid: 19118200
20	J Jiang, J Wang, M Yue, X Cai, T Wang, C Wu, H Su, Y Wang, M Han, Y Zhang, X Zhu, P Jiang, P Li, Y Sun, W Xiao, H Feng, G Qing, H Liu. Direct phosphorylation and stabilization of MYC by Aurora B kinase promote T-cell leukemogenesis. Cancer Cell 2020; 37(2): 200–215.e5 https://doi.org/10.1016/j.ccell.2020.01.001 pmid: 32049046
21	M Sanchez-Martin, A Ferrando. The NOTCH1-MYC highway toward T-cell acute lymphoblastic leukemia. Blood 2017; 129(9): 1124–1133 https://doi.org/10.1182/blood-2016-09-692582 pmid: 28115368
22	MY Chiang, Q Wang, AC Gormley, SJ Stein, L Xu, O Shestova, JC Aster, WS Pear. High selective pressure for Notch1 mutations that induce Myc in T-cell acute lymphoblastic leukemia. Blood 2016; 128(18): 2229–2240 https://doi.org/10.1182/blood-2016-01-692855 pmid: 27670423
23	M Loosveld, R Castellano, S Gon, A Goubard, T Crouzet, L Pouyet, T Prebet, N Vey, B Nadel, Y Collette, D Payet-Bornet. Therapeutic targeting of c-Myc in T-cell acute lymphoblastic leukemia, T-ALL. Oncotarget 2014; 5(10): 3168–3172 https://doi.org/10.18632/oncotarget.1873 pmid: 24930440
24	MR McKeown, JE Bradner. Therapeutic strategies to inhibit MYC. Cold Spring Harb Perspect Med 2014; 4(10): a014266 https://doi.org/10.1101/cshperspect.a014266 pmid: 25274755
25	M Beyer, A Romanski, AM Mustafa, M Pons, I Büchler, A Vogel, A Pautz, A Sellmer, G Schneider, G Bug, OH Krämer. HDAC3 activity is essential for human leukemic cell growth and the expression of β-catenin, MYC, and WT1. Cancers (Basel) 2019; 11(10): 1436 https://doi.org/10.3390/cancers11101436 pmid: 31561534
26	K Sun, R Atoyan, MA Borek, S Dellarocca, ME Samson, AW Ma, GX Xu, T Patterson, DP Tuck, JL Viner, A Fattaey, J Wang. Dual HDAC and PI3K inhibitor CUDC-907 downregulates MYC and suppresses growth of MYC-dependent cancers. Mol Cancer Ther 2017; 16(2): 285–299 https://doi.org/10.1158/1535-7163.MCT-16-0390 pmid: 27980108
27	M Waibel, SJ Vervoort, IY Kong, S Heinzel, KM Ramsbottom, BP Martin, ED Hawkins, RW Johnstone. Epigenetic targeting of Notch1-driven transcription using the HDACi panobinostat is a potential therapy against T-cell acute lymphoblastic leukemia. Leukemia 2018; 32(1): 237–241 https://doi.org/10.1038/leu.2017.282 pmid: 28914259
28	F Ferrante, BD Giaimo, M Bartkuhn, T Zimmermann, V Close, D Mertens, A Nist, T Stiewe, J Meier-Soelch, M Kracht, S Just, P Klöble, F Oswald, T Borggrefe. HDAC3 functions as a positive regulator in Notch signal transduction. Nucleic Acids Res 2020; 48(7): 3496–3512 https://doi.org/10.1093/nar/gkaa088 pmid: 32107550
29	N Reynoird, BE Schwartz, M Delvecchio, K Sadoul, D Meyers, C Mukherjee, C Caron, H Kimura, S Rousseaux, PA Cole, D Panne, CA French, S Khochbin. Oncogenesis by sequestration of CBP/p300 in transcriptionally inactive hyperacetylated chromatin domains. EMBO J 2010; 29(17): 2943–2952 https://doi.org/10.1038/emboj.2010.176 pmid: 20676058
30	JE Delmore, GC Issa, ME Lemieux, PB Rahl, J Shi, HM Jacobs, E Kastritis, T Gilpatrick, RM Paranal, J Qi, M Chesi, AC Schinzel, MR McKeown, TP Heffernan, CR Vakoc, PL Bergsagel, IM Ghobrial, PG Richardson, RA Young, WC Hahn, KC Anderson, AL Kung, JE Bradner, CS Mitsiades. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011; 146(6): 904–917 https://doi.org/10.1016/j.cell.2011.08.017 pmid: 21889194
31	PS Suresh, VC Devaraj, NR Srinivas, R Mullangi. Review of bioanalytical assays for the quantitation of various HDAC inhibitors such as vorinostat, belinostat, panobinostat, romidepsin and chidamine. Biomed Chromatogr 2017; 31(1): e3807 https://doi.org/10.1002/bmc.3807 pmid: 27511598
32	Z Liu, K Ding, L Li, H Liu, Y Wang, C Liu, R Fu. A novel histone deacetylase inhibitor chidamide induces G0/G1 arrest and apoptosis in myelodysplastic syndromes. Biomed Pharmacother 2016; 83: 1032–1037 https://doi.org/10.1016/j.biopha.2016.08.023 pmid: 27541047
33	S Zhao, J Guo, Y Zhao, C Fei, Q Zheng, X Li, C Chang. Chidamide, a novel histone deacetylase inhibitor, inhibits the viability of MDS and AML cells by suppressing JAK2/STAT3 signaling. Am J Transl Res 2016; 8(7): 3169–3178 pmid: 27508038
34	T Jiang, F Wang, L Hu, X Cheng, Y Zheng, T Liu, Y Jia. Chidamide and decitabine can synergistically induce apoptosis of Hodgkin lymphoma cells by up-regulating the expression of PU.1 and KLF4. Oncotarget 2017; 8(44): 77586–77594 https://doi.org/10.18632/oncotarget.20659 pmid: 29100410
35	J He, Q Chen, H Gu, J Chen, E Zhang, X Guo, X Huang, H Yan, D He, Y Yang, Y Zhao, G Wang, H He, Q Yi, Z Cai. Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease. Haematologica 2018; 103(8): 1369–1379 https://doi.org/10.3324/haematol.2017.181172 pmid: 29773595
36	J Zhou, C Zhang, X Sui, S Cao, F Tang, S Sun, S Wang, B Chen. Histone deacetylase inhibitor chidamide induces growth inhibition and apoptosis in NK/T lymphoma cells through ATM-Chk2-p53-p21 signalling pathway. Invest New Drugs 2018; 36(4): 571–580 https://doi.org/10.1007/s10637-017-0552-y pmid: 29504068
37	Y Shi, B Jia, W Xu, W Li, T Liu, P Liu, W Zhao, H Zhang, X Sun, H Yang, X Zhang, J Jin, Z Jin, Z Li, L Qiu, M Dong, X Huang, Y Luo, X Wang, X Wang, J Wu, J Xu, P Yi, J Zhou, H He, L Liu, J Shen, X Tang, J Wang, J Yang, Q Zeng, Z Zhang, Z Cai, X Chen, K Ding, M Hou, H Huang, X Li, R Liang, Q Liu, Y Song, H Su, Y Gao, L Liu, J Luo, L Su, Z Sun, H Tan, H Wang, J Wang, S Wang, H Zhang, X Zhang, D Zhou, O Bai, G Wu, L Zhang, Y Zhang. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol 2017; 10(1): 69 https://doi.org/10.1186/s13045-017-0439-6 pmid: 28298231
38	X Lu, Z Ning, Z Li, H Cao, X Wang. Development of chidamide for peripheral T-cell lymphoma, the first orphan drug approved in China. Intractable Rare Dis Res 2016; 5(3): 185–191 https://doi.org/10.5582/irdr.2016.01024 pmid: 27672541
39	W Guan, Y Jing, L Dou, M Wang, Y Xiao, L Yu. Chidamide in combination with chemotherapy in refractory and relapsed T lymphoblastic lymphoma/leukemia. Leuk Lymphoma 2020; 61(4): 855–861 https://doi.org/10.1080/10428194.2019.1691195 pmid: 31755348
40	XQ Weng, Y Shen, Y Sheng, B Chen, JH Wang, JM Li, JQ Mi, QS Chen, YM Zhu, CL Jiang, H Yan, XX Zhang, T Huang, Z Zhu, Z Chen, SJ Chen. Prognostic significance of monitoring leukemia-associated immunophenotypes by eight-color flow cytometry in adult B-acute lymphoblastic leukemia. Blood Cancer J 2013; 3(8): e133 https://doi.org/10.1038/bcj.2013.31 pmid: 23955588
41	YM Zhu, WL Zhao, JF Fu, JY Shi, Q Pan, J Hu, XD Gao, B Chen, JM Li, SM Xiong, LJ Gu, JY Tang, H Liang, H Jiang, YQ Xue, ZX Shen, Z Chen, SJ Chen. NOTCH1 mutations in T-cell acute lymphoblastic leukemia: prognostic significance and implication in multifactorial leukemogenesis. Clin Cancer Res 2006; 12(10): 3043–3049 https://doi.org/10.1158/1078-0432.CCR-05-2832 pmid: 16707600
42	A Dobin, CA Davis, F Schlesinger, J Drenkow, C Zaleski, S Jha, P Batut, M Chaisson, TR Gingeras. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013; 29(1): 15–21 https://doi.org/10.1093/bioinformatics/bts635 pmid: 23104886
43	S Anders, PT Pyl, W Huber. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 2015; 31(2): 166–169 https://doi.org/10.1093/bioinformatics/btu638 pmid: 25260700
44	H Varet, L Brillet-Guéguen, JY Coppée, MA Dillies. SARTools: a DESeq2- and EdgeR-based R pipeline for comprehensive differential analysis of RNA-Seq data. PLoS One 2016; 11(6): e0157022 https://doi.org/10.1371/journal.pone.0157022 pmid: 27280887
45	JJ Xu, FR Yao, M Jiang, YT Zhang, F Guo. High-resolution melting analysis for rapid and sensitive NOTCH1 screening in chronic lymphocytic leukemia. Int J Mol Med 2017; 39(2): 415–422 https://doi.org/10.3892/ijmm.2017.2849 pmid: 28075457
46	B Squiban, ST Ahmed, JK Frazer. Creation of a human T-ALL cell line online database. Leuk Lymphoma 2017; 58(11): 2728–2730 https://doi.org/10.1080/10428194.2017.1300896 pmid: 28609209
47	ML Sulis, O Williams, T Palomero, V Tosello, S Pallikuppam, PJ Real, K Barnes, L Zuurbier, JP Meijerink, AA Ferrando. NOTCH1 extracellular juxtamembrane expansion mutations in T-ALL. Blood 2008; 112(3): 733–740 https://doi.org/10.1182/blood-2007-12-130096 pmid: 18411416
48	L Horvat, M Antica, M Matulić. Effect of Notch and PARP pathways’ inhibition in leukemic cells. Cells 2018; 7(6): 58 https://doi.org/10.3390/cells7060058 pmid: 29903986
49	CY Gui, L Ngo, WS Xu, VM Richon, PA Marks. Histone deacetylase (HDAC) inhibitor activation of p21WAF1 involves changes in promoter-associated proteins, including HDAC1. Proc Natl Acad Sci USA 2004; 101(5): 1241–1246 https://doi.org/10.1073/pnas.0307708100 pmid: 14734806
50	KR Stengel, SW Hiebert. Class I HDACs affect DNA replication, repair, and chromatin structure: implications for cancer therapy. Antioxid Redox Signal 2015; 23(1): 51–65 https://doi.org/10.1089/ars.2014.5915 pmid: 24730655
51	J Boulaire, A Fotedar, R Fotedar. The functions of the cdk-cyclin kinase inhibitor p21WAF1. Pathol Biol (Paris) 2000; 48(3): 190–202 pmid: 10858953
52	F Radtke, A Wilson, SJ Mancini, HR MacDonald. Notch regulation of lymphocyte development and function. Nat Immunol 2004; 5(3): 247–253 https://doi.org/10.1038/ni1045 pmid: 14985712
53	BA Osborne, LM Minter. Notch signalling during peripheral T-cell activation and differentiation. Nat Rev Immunol 2007; 7(1): 64–75 https://doi.org/10.1038/nri1998 pmid: 17170755
54	VW Yu, B Saez, C Cook, S Lotinun, A Pardo-Saganta, YH Wang, S Lymperi, F Ferraro, MH Raaijmakers, JY Wu, L Zhou, J Rajagopal, HM Kronenberg, R Baron, DT Scadden. Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow. J Exp Med 2015; 212(5): 759–774 https://doi.org/10.1084/jem.20141843 pmid: 25918341
55	F Malard, M Mohty. Acute lymphoblastic leukaemia. Lancet 2020; 395(10230): 1146–1162 https://doi.org/10.1016/S0140-6736(19)33018-1 pmid: 32247396
56	J De Bie, S Demeyer, L Alberti-Servera, E Geerdens, H Segers, M Broux, K De Keersmaecker, L Michaux, P Vandenberghe, T Voet, N Boeckx, A Uyttebroeck, J Cools. Single-cell sequencing reveals the origin and the order of mutation acquisition in T-cell acute lymphoblastic leukemia. Leukemia 2018; 32(6): 1358–1369 https://doi.org/10.1038/s41375-018-0127-8 pmid: 29740158
57	G Roti, J Qi, S Kitara, M Sanchez-Martin, A Saur Conway, AC Varca, A Su, L Wu, AL Kung, AA Ferrando, JE Bradner, K Stegmaier. Leukemia-specific delivery of mutant NOTCH1 targeted therapy. J Exp Med 2018; 215(1): 197–216 https://doi.org/10.1084/jem.20151778 pmid: 29158376
58	D Herranz, A Ambesi-Impiombato, T Palomero, SA Schnell, L Belver, AA Wendorff, L Xu, M Castillo-Martin, D Llobet-Navás, C Cordon-Cardo, E Clappier, J Soulier, AAA Ferrando. A NOTCH1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med 2014; 20(10): 1130–1137 https://doi.org/10.1038/nm.3665 pmid: 25194570
59	D Herranz, AA Ferrando. An oncogenic enhancer enemy (N-Me) in T-ALL. Cell Cycle 2015; 14(2): 167–168 https://doi.org/10.4161/15384101.2014.989129 pmid: 25584678
60	D Sengupta, A Kannan, M Kern, MA Moreno, E Vural, B Stack Jr, JY Suen, AJ Tackett, L Gao. Disruption of BRD4 at H3K27Ac-enriched enhancer region correlates with decreased c-Myc expression in Merkel cell carcinoma. Epigenetics 2015; 10(6): 460–466 https://doi.org/10.1080/15592294.2015.1034416 pmid: 25941994
61	J Lovén, HA Hoke, CY Lin, A Lau, DA Orlando, CR Vakoc, JE Bradner, TI Lee, RA Young. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013; 153(2): 320–334 https://doi.org/10.1016/j.cell.2013.03.036 pmid: 23582323
62	D Levens, PD Aplan. Notching up MYC gives a LIC. Cell Stem Cell 2013; 13(1): 8–9 https://doi.org/10.1016/j.stem.2013.06.008 pmid: 23827704
63	CW Cheng, M Biton, AL Haber, N Gunduz, G Eng, LT Gaynor, S Tripathi, G Calibasi-Kocal, S Rickelt, VL Butty, M Moreno-Serrano, AM Iqbal, KE Bauer-Rowe, S Imada, MS Ulutas, C Mylonas, MT Whary, SS Levine, Y Basbinar, RO Hynes, M Mino-Kenudson, V Deshpande, LA Boyer, JG Fox, C Terranova, K Rai, H Piwnica-Worms, MM Mihaylova, A Regev, OH Yilmaz. Ketone body signaling mediates intestinal stem cell homeostasis and adaptation to diet. Cell 2019; 178(5): 1115–1131.e15 https://doi.org/10.1016/j.cell.2019.07.048 pmid: 31442404

[1]

FMD-21031-OF-MJQ_suppl_1

Download

Viewed

Full text

Abstract

Cited

Shared

Discussed