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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

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2018 Impact Factor: 1.847

Front. Med.    2015, Vol. 9 Issue (1) : 1-9    https://doi.org/10.1007/s11684-015-0381-3
REVIEW
Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia
Ching-Hon Pui()
Departments of Oncology and Pathology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA; the University of Tennessee Health Science Center, Memphis, TN 38105, USA
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Abstract

With the cure rate of childhood acute lymphoblastic leukemia (ALL) approaching 90%, further improvement in the treatment outcome and quality of life of patients will require better understanding of the mechanisms of drug resistance, identifying new leukemic cell genetic lesions that are amendable to available target therapy, and optimizing treatment based on host pharmacodynamics and pharmacogenomics. Deeper characterization of leukemic cell genetic abnormalities has discovered new subtypes of leukemia such as early T-cell precursor ALL and Philadelphia chromosome-like ALL, and identified many genomic alterations that have diagnostic, prognostic, or therapeutic implications. In this regard, several novel fusion transcripts are responsive to ABL tyrosine kinase inhibitors and potentially to JAK inhibitors. Genome-wide analyses have also unraveled the role of inherited cancer predisposing genes and small nucleotide polymorphisms of several genes in the development of childhood ALL. These advances promise to lead to more sophisticated personalized treatment strategies in the near future.

Keywords pharmacogenomics      acute lymphoblastic leukemia      genomics      pharmacogenetics     
Corresponding Author(s): Ching-Hon Pui   
Online First Date: 12 December 2014    Issue Date: 02 March 2015
 Cite this article:   
Ching-Hon Pui. Genomic and pharmacogenetic studies of childhood acute lymphoblastic leukemia[J]. Front. Med., 2015, 9(1): 1-9.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-015-0381-3
https://academic.hep.com.cn/fmd/EN/Y2015/V9/I1/1
White/Non-black (%) Black (%)
Hyperdiploidy>50 28.2 11.4
ETV6-RUNX1 18.6 21.5
BCR-ABL1-like 8.8 3.8
TCF3-PBX1 4.1 13.9
ERG 3.1 1.3
Hypodiploidy 2.6 -
BCR-ABL1 1.7 3.8
Rearranged MLL 1.4 3.8
CRLF2 (not BCR-ABL1-like) 1.7 1.3
Other B 16.0 20.3
T-cell 12.6 12.7
Early T-cell precursor 1.2 6.3
Tab.1  Estimated frequency of specific subtypes of ALL by race in patients treated at St. Jude Children’s Research Hospital between 2000 and 2007
Study group Ethnic study population Sample size (n) Susceptibility loci Comment References
COG, SJCRH Caucasian 441 ARID5BIKZF1 ARID5B associated with hyperdiploid ALL Trevi?o et al. [23]
UKCCS, MRS Caucasian 907 ARID5BIKZF1CEBPE ARID5B associated with hyperdiploid ALL Papaemmanuil et al. [24]
UK, BFM, Spain, Hungary, Canada Caucasian 3293 ARID5BIKZF1CEBPECDKN2A CDKN2A associated with both B- and T-ALL Sherborne et al. [25]
COG, SJCRH Caucasian, Black, Hispanic 2450 ARID5BIKZF1CEBPECDKN2ABMI1-PIP4K2A The number of risk alleles associated positively with the risk of ALL Xu et al. [26]
AIEOP, BFM, COALL Caucasian 1370 TP63PTPRJ TP63 and PTPRJ associated with ETV6-RUNX1-rearranged ALL. Ellinghaus et al. [28]
COG, SJCRH Caucasian, Black, Hispanic 682 GATA3 GATA3 associated with Philadelphia chromosome-like ALL and poor prognosis Perez-Andreu et al. [29]
UKCCS, MRC UKALL, BFM Caucasian 3107 ARID5BIKZF1CEBPECDKN2ABMI1-PIP4K2AGATA3 GATA3 associated with increased risk of ALL risk and poor prognosis Migliorini et al. [30]
Tab.2  Genome-wide association of studies of susceptibility of childhood acute lymphoblastic leukemia
Drug Genes Comments References
Asparaginase HLA-DRB1*07:01 HLA-DRB1*07:01-encoded protein is associated with higher incidence of the development of anti-asparaginase antibody and a higher frequency of asparaginase hypersensitivity, probably through its high-affinity binding to asparaginase epitopes. Christian et al. [37]
Methotrexate SLCO1B1 Methotrexate clearance is associated with polymorphisms of SLCO1B1 which encode a hepatic solute carrier organic anion transporter that mediates disposition of many medications including methotrexate. Ramsey et al. [38,39]
Mercaptopurine TPMT, PACSIN2 Genetic polymorphisms in TPMT (thiopurine S-methyltransferase) are known to have a marked effect on mercaptopurine metabolism and toxicity. By modulating TPMT activity, polymorphism in PACSIN2 (protein kinase C and casein kinase substrate in neurons protein 2) increases the severity of gastrointestinal toxicity associated with mercaptopurine therapy. Stocco et al. [40]
Corticosteroids CRHR1 Polymorphisms of CRHR1 that encodes corticotropin-releasing hormone receptor-1 are associated with low bone density in male patients treated with corticosteroids, probably due to its effect on the release of corticotropin from the anterior pituitary, altering levels of circulating endogenous glucocorticoids. Jones et al. [41]
Corticosteroids PAI-1 A polymorphism of PAI-1 that encodes plasminogen activator inhibitor-1 is associated with increased risk of dexamethasone-related osteonecrosis. It was speculated that high levels of PAI-1, by inhibiting fibrinolysis and resulting increased intraosseous venous pressure blocking blood flow to the bone, cause osteonecrosis. French et al. [42]
Anthracycline HAS3 A variant of hyaluronan synthase 3 gene is associated with increased risk of anthracycline-related cardiomyopathy, which could be due to inadequate remodeling or inadequate protection of the heart from reactive oxygen species after anthracycline treatment. Wang et al. [43]
Vincristine CEP72 A polymorphism of CEP72 reduces expression of its encoded centrosomal protein 72kDa that functions as the major microtubule-organizing center and regulates proper bipolar spindle formation and is associated with an increased risk of vincristine-induced neuropathy. Diouf et al. [44]
Tab.3  Selected examples of genomic determinants of drug toxicities
1 Pui CH, Evans WE. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol 2013; 50(3): 185–196
https://doi.org/10.1053/j.seminhematol.2013.06.007 pmid: 23953334
2 Pui CH, Pei D, Campana D, Cheng C, Sandlund JT, Bowman WP, Hudson MM, Ribeiro RC, Raimondi SC, Jeha S, Howard SC, Bhojwani D, Inaba H, Rubnitz JE, Metzger ML, Gruber TA, Coustan-Smith E, Downing JR, Leung WH, Relling MV, Evans WE. A revised definition for cure of childhood acute lymphoblastic leukemia. Leukemia 2014 Apr 30. [Epub ahead of print]
https://doi.org/10.1038/leu.2014.142 pmid: 24781017
3 Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood 2012; 120(6): 1165–1174
https://doi.org/10.1182/blood-2012-05-378943 pmid: 22730540
4 Mullighan CG. Genome sequencing of lymphoid malignancies. Blood 2013; 122(24): 3899–3907
https://doi.org/10.1182/blood-2013-08-460311 pmid: 24041576
5 Relling MV, Ramsey LB. Pharmacogenomics of acute lymphoid leukemia: new insights into treatment toxicity and efficacy. Hematology (Am Soc Hematol Educ Program)2013; 2013(1): 126–130
https://doi.org/10.1182/asheducation-2013.1.126 pmid: 24319173
6 Coustan-Smith E, Mullighan CG, Onciu M, Behm FG, Raimondi SC, Pei D, Cheng C, Su X, Rubnitz JE, Basso G, Biondi A, Pui CH, Downing JR, Campana D. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009; 10(2): 147–156
https://doi.org/10.1016/S1470-2045(08)70314-0 pmid: 19147408
7 Zhang J, Ding L, Holmfeldt L, Wu G, Heatley SL, Payne-Turner D, Easton J, Chen X, Wang J, Rusch M, Lu C, Chen SC, Wei L, Collins-Underwood JR, Ma J, Roberts KG, Pounds SB, Ulyanov A, Becksfort J, Gupta P, Huether R, Kriwacki RW, Parker M, McGoldrick DJ, Zhao D, Alford D, Espy S, Bobba KC, Song G, Pei D, Cheng C, Roberts S, Barbato MI, Campana D, Coustan-Smith E, Shurtleff SA, Raimondi SC, Kleppe M, Cools J, Shimano KA, Hermiston ML, Doulatov S, Eppert K, Laurenti E, Notta F, Dick JE, Basso G, Hunger SP, Loh ML, Devidas M, Wood B, Winter S, Dunsmore KP, Fulton RS, Fulton LL, Hong X, Harris CC, Dooling DJ, Ochoa K, Johnson KJ, Obenauer JC, Evans WE, Pui CH, Naeve CW, Ley TJ, Mardis ER, Wilson RK, Downing JR, Mullighan CG. The genetic basis of early T-cell precursor acute lymphoblastic leukaemia. Nature 2012; 481(7380): 157–163
https://doi.org/10.1038/nature10725 pmid: 22237106
8 Mullighan CG, Su X, Zhang J, Radtke I, Phillips LA, Miller CB, Ma J, Liu W, Cheng C, Schulman BA, Harvey RC, Chen IM, Clifford RJ, Carroll WL, Reaman G, Bowman WP, Devidas M, Gerhard DS, Yang W, Relling MV, Shurtleff SA, Campana D, Borowitz MJ, Pui CH, Smith M, Hunger SP, Willman CL, Downing JR; Children’s Oncology Group. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 2009; 360(5): 470–480
https://doi.org/10.1056/NEJMoa0808253 pmid: 19129520
9 Den Boer ML, van Slegtenhorst M, De Menezes RX, Cheok MH, Buijs-Gladdines JG, Peters ST, Van Zutven LJ, Beverloo HB, Van der Spek PJ, Escherich G, Horstmann MA, Janka-Schaub GE, Kamps WA, Evans WE, Pieters R. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009; 10(2): 125–134
https://doi.org/10.1016/S1470-2045(08)70339-5 pmid: 19138562
10 van der Veer A, Waanders E, Pieters R, Willemse ME, Van Reijmersdal SV, Russell LJ, Harrison CJ, Evans WE, van der Velden VH, Hoogerbrugge PM, Van Leeuwen F, Escherich G, Horstmann MA, Mohammadi Khankahdani L, Rizopoulos D, De Groot-Kruseman HA, Sonneveld E, Kuiper RP, Den Boer ML. Independent prognostic value of BCR-ABL1-like signature and IKZF1 deletion, but not high CRLF2 expression, in children with B-cell precursor ALL. Blood 2013; 122(15): 2622–2629
https://doi.org/10.1182/blood-2012-10-462358 pmid: 23974192
11 Loh ML, Zhang J, Harvey RC, Roberts K, Payne-Turner D, Kang H, Wu G, Chen X, Becksfort J, Edmonson M, Buetow KH, Carroll WL, Chen IM, Wood B, Borowitz MJ, Devidas M, Gerhard DS, Bowman P, Larsen E, Winick N, Raetz E, Smith M, Downing JR, Willman CL, Mullighan CG, Hunger SP. Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children’s Oncology Group TARGET Project. Blood 2013; 121(3): 485–488
https://doi.org/10.1182/blood-2012-04-422691 pmid: 23212523
12 Roberts KG, Pei D, Campana D, Payne-Turner D, Li Y, Cheng C, Sandlund JT, Jeha S, Easton J, Becksfort J, Zhang J, Coustan-Smith E, Raimondi SC, Leung WH, Relling MV, Evans WE, Downing JR, Mullighan CG, Pui CH. Outcome of children with BCR-ABL1-like acute lymphoblastic leukemia treated with risk-directed therapy based on the levels of minimal residual disease. J Clin Oncol 2014; 32(27): 3012–3020
https://doi.org/10.1200/JCO.2014.55.4105 pmid: 25049327
13 Weston BW, Hayden MA, Roberts KG, Bowyer S, Hsu J, Fedoriw G, Rao KW, Mullighan CG. Tyrosine kinase inhibitor therapy induces remission in a patient with refractory EBF1-PDGFRB-positive acute lymphoblastic leukemia. J Clin Oncol 2013; 31(25): e413–e416
https://doi.org/10.1200/JCO.2012.47.6770 pmid: 23835704
14 Lengline E, Beldjord K, Dombret H, Soulier J, Boissel N, Clappier E. Successful tyrosine kinase inhibitor therapy in a refractory B-cell precursor acute lymphoblastic leukemia with EBF1-PDGFRB fusion. Haematologica 2013; 98(11): e146–e148
https://doi.org/10.3324/haematol.2013.095372 pmid: 24186319
15 Roberts KG, Li Y, Payne-Turner D, Harvey RC, Yang YL, Pei D, McCastlain K, Ding L, Lu C, Song G, Ma J, Becksfort J, Rusch M, Chen SC, Easton J, Cheng J, Boggs K, Santiago-Morales N, Iacobucci I, Fulton RS, Wen J, Valentine M, Cheng C, Paugh SW, Devidas M, Chen IM, Reshmi S, Smith A, Hedlund E, Gupta P, Nagahawatte P, Wu G, Chen X, Yergeau D, Vadodaria B, Mulder H, Winick NJ, Larsen EC, Carroll WL, Heerema NA, Carroll AJ, Grayson G, Tasian SK, Moore AS, Keller F, Frei-Jones M, Whitlock JA, Raetz EA, White DL, Hughes TP, Guidry Auvil JM, Smith MA, Marcucci G, Bloomfield CD, Mrózek K, Kohlschmidt J, Stock W, Kornblau SM, Konopleva M, Paietta E, Pui CH, Jeha S, Relling MV, Evans WE, Gerhard DS, Gastier-Foster JM, Mardis E, Wilson RK, Loh ML, Downing JR, Hunger SP, Willman CL, Zhang J, Mullighan CG. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med 2014; 371(11): 1005–1015
pmid: 25207766
16 Pui CH, Williams DL, Raimondi SC, Rivera GK, Look AT, Dodge RK, George SL, Behm FG, Crist WM, Murphy SB. Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia. Blood 1987; 70(1): 247–253
pmid: 3474042
17 Pui CH, Carroll AJ, Raimondi SC, Land VJ, Crist WM, Shuster JJ, Williams DL, Pullen DJ, Borowitz MJ, Behm FG, . Clinical presentation, karyotypic characterization, and treatment outcome of childhood acute lymphoblastic leukemia with a near-haploid or hypodiploid less than 45 line. Blood 1990; 75(5): 1170–1177
pmid: 2306521
18 Harrison CJ, Moorman AV, Broadfield ZJ, Cheung KL, Harris RL, Reza Jalali G, Robinson HM, Barber KE, Richards SM, Mitchell CD, Eden TO, Hann IM, Hill FG, Kinsey SE, Gibson BE, Lilleyman J, Vora A, Goldstone AH, Franklin IM, Durrant J, Martineau M; Childhood and Adult Leukaemia Working Parties. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. Br J Haematol 2004; 125(5): 552–559
https://doi.org/10.1111/j.1365-2141.2004.04948.x pmid: 15147369
19 Nachman JB, Heerema NA, Sather H, Camitta B, Forestier E, Harrison CJ, Dastugue N, Schrappe M, Pui CH, Basso G, Silverman LB, Janka-Schaub GE. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 2007; 110(4): 1112–1115
https://doi.org/10.1182/blood-2006-07-038299 pmid: 17473063
20 Holmfeldt L, Wei L, Diaz-Flores E, Walsh M, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen SC, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Phillips LA, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Vadodaria B, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Huether R, Lu C, Fulton RS, Fulton LL, Tabib Y, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Roberts AW, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Ellison DW, Shurtleff SA, Pui CH, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG. The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nat Genet 2013; 45(3): 242–252
https://doi.org/10.1038/ng.2532 pmid: 23334668
21 Mühlbacher V, Zenger M, Schnittger S, Weissmann S, Kunze F, Kohlmann A, Bellos F, Kern W, Haferlach T, Haferlach C. Acute lymphoblastic leukemia with low hypodiploid/near triploid karyotype is a specific clinical entity and exhibits a very high TP53 mutation frequency of 93%. Genes Chromosomes Cancer 2014; 53(6): 524–536
https://doi.org/10.1002/gcc.22163 pmid: 24619868
22 Shah S, Schrader KA, Waanders E, Timms AE, Vijai J, Miething C, Wechsler J, Yang J, Hayes J, Klein RJ, Zhang J, Wei L, Wu G, Rusch M, Nagahawatte P, Ma J, Chen SC, Song G, Cheng J, Meyers P, Bhojwani D, Jhanwar S, Maslak P, Fleisher M, Littman J, Offit L, Rau-Murthy R, Fleischut MH, Corines M, Murali R, Gao X, Manschreck C, Kitzing T, Murty VV, Raimondi SC, Kuiper RP, Simons A, Schiffman JD, Onel K, Plon SE, Wheeler DA, Ritter D, Ziegler DS, Tucker K, Sutton R, Chenevix-Trench G, Li J, Huntsman DG, Hansford S, Senz J, Walsh T, Lee M, Hahn CN, Roberts KG, King MC, Lo SM, Levine RL, Viale A, Socci ND, Nathanson KL, Scott HS, Daly M, Lipkin SM, Lowe SW, Downing JR, Altshuler D, Sandlund JT, Horwitz MS, Mullighan CG, Offit K. A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia. Nat Genet 2013; 45(10): 1226–1231
https://doi.org/10.1038/ng.2754 pmid: 24013638
23 Trevi?o LR, Yang W, French D, Hunger SP, Carroll WL, Devidas M, Willman C, Neale G, Downing J, Raimondi SC, Pui CH, Evans WE, Relling MV. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet 2009; 41(9): 1001–1005
24 Papaemmanuil E, Hosking FJ, Vijayakrishnan J, Price A, Olver B, Sheridan E, Kinsey SE, Lightfoot T, Roman E, Irving JA, Allan JM, Tomlinson IP, Taylor M, Greaves M, Houlston RS. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet 2009; 41(9): 1006–1010,
25 Sherborne AL, Hosking FJ, Prasad RB, Kumar R, Koehler R, Vijayakrishnan J, Papaemmanuil E, Bartram CR, Stanulla M, Schrappe M, Gast A, Dobbins SE, Ma Y, Sheridan E, Taylor M, Kinsey SE, Lightfoot T, Roman E, Irving JA, Allan JM, Moorman AV, Harrison CJ, Tomlinson IP, Richards S, Zimmermann M, Szalai C, Semsei AF, Erdelyi DJ, Krajinovic M, Sinnett D, Healy J, Gonzalez Neira A, Kawamata N, Ogawa S, Koeffler HP, Hemminki K, Greaves M, Houlston RS. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet 2010; 42(6): 492–494
https://doi.org/10.1038/ng.585 pmid: 20453839
26 Xu H, Yang W, Perez-Andreu V, Devidas M, Fan Y, Cheng C, Pei D, Scheet P, Burchard EG, Eng C, Huntsman S, Torgerson DG, Dean M, Winick NJ, Martin PL, Camitta BM, Bowman WP, Willman CL, Carroll WL, Mullighan CG, Bhojwani D, Hunger SP, Pui CH, Evans WE, Relling MV, Loh ML, Yang JJ. Novel susceptibility variants at 10p12.31-12.2 for childhood acute lymphoblastic leukemia in ethnically diverse populations. J Natl Cancer Inst 2013; 105(10): 733–742
https://doi.org/10.1093/jnci/djt042 pmid: 23512250
27 Mullighan CG, Goorha S, Radtke I, Miller CB, Coustan-Smith E, Dalton JD, Girtman K, Mathew S, Ma J, Pounds SB, Su X, Pui CH, Relling MV, Evans WE, Shurtleff SA, Downing JR. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007; 446(7137): 758–764
https://doi.org/10.1038/nature05690 pmid: 17344859
28 Ellinghaus E, Stanulla M, Richter G, Ellinghaus D, te Kronnie G, Cario G, Cazzaniga G, Horstmann M, Panzer Grümayer R, Cavé H, Trka J, Cinek O, Teigler-Schlegel A, ElSharawy A, H?sler R, Nebel A, Meissner B, Bartram T, Lescai F, Franceschi C, Giordan M, Nürnberg P, Heinzow B, Zimmermann M, Schreiber S, Schrappe M, Franke A. Identification of germline susceptibility loci in ETV6-RUNX1-rearranged childhood acute lymphoblastic leukemia. Leukemia 2012; 26(5): 902–909
https://doi.org/10.1038/leu.2011.302 pmid: 22076464
29 Perez-Andreu V, Roberts KG, Harvey RC, Yang W, Cheng C, Pei D, Xu H, Gastier-Foster J, e S, Lim JY, Chen IM, Fan Y, Devidas M, Borowitz MJ, Smith C, Neale G, Burchard EG, Torgerson DG, Klussmann FA, Villagran CR, Winick NJ, Camitta BM, Raetz E, Wood B, Yue F, Carroll WL, Larsen E, Bowman WP, Loh ML, Dean M, Bhojwani D, Pui CH, Evans WE, Relling MV, Hunger SP, Willman CL, Mullighan CG, Yang JJ. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse. Nat Genet 2013; 45(12): 1494–1498
https://doi.org/10.1038/ng.2803 pmid: 24141364
30 Migliorini G, Fiege B, Hosking FJ, Ma Y, Kumar R, Sherborne AL, da Silva Filho MI, Vijayakrishnan J, Koehler R, Thomsen H, Irving JA, Allan JM, Lightfoot T, Roman E, Kinsey SE, Sheridan E, Thompson P, Hoffmann P, N?then MM, Mühleisen TW, Eisele L, Zimmermann M, Bartram CR, Schrappe M, Greaves M, Stanulla M, Hemminki K, Houlston RS. Variation at 10p12.2 and 10p14 influences risk of childhood B-cell acute lymphoblastic leukemia and phenotype. Blood 2013; 122(19): 3298–3307
https://doi.org/10.1182/blood-2013-03-491316 pmid: 23996088
31 Holleman A, Cheok MH, den Boer ML, Yang W, Veerman AJ, Kazemier KM, Pei D, Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med 2004; 351(6): 533–542
https://doi.org/10.1056/NEJMoa033513 pmid: 15295046
32 Lugthart S, Cheok MH, den Boer ML, Yang W, Holleman A, Cheng C, Pui CH, Relling MV, Janka-Schaub GE, Pieters R, Evans WE. Identification of genes associated with chemotherapy crossresistance and treatment response in childhood acute lymphoblastic leukemia. Cancer Cell 2005; 7(4): 375–386
https://doi.org/10.1016/j.ccr.2005.03.002 pmid: 15837626
33 Sorich MJ, Pottier N, Pei D, Yang W, Kager L, Stocco G, Cheng C, Panetta JC, Pui CH, Relling MV, Cheok MH, Evans WE. In vivo response to methotrexate forecasts outcome of acute lymphoblastic leukemia and has a distinct gene expression profile. PLoS Med 2008; 5(4): e83 10.1371
https://doi.org/10.1371
34 Yang JJ, Cheng C, Yang W, Pei D, Cao X, Fan Y, Pounds SB, Neale G, Trevi?o LR, French D, Campana D, Downing JR, Evans WE, Pui CH, Devidas M, Bowman WP, Camitta BM, Willman CL, Davies SM, Borowitz MJ, Carroll WL, Hunger SP, Relling MV. Genome-wide interrogation of germline genetic variation associated with treatment response in childhood acute lymphoblastic leukemia. JAMA 2009; 301(4): 393–403
https://doi.org/10.1001/jama.2009.7 pmid: 19176441
35 Trevi?o LR, Shimasaki N, Yang W, Panetta JC, Cheng C, Pei D, Chan D, Sparreboom A, Giacomini KM, Pui CH, Evans WE, Relling MV. Germline genetic variation in an organic anion transporter polypeptide associated with methotrexate pharmacokinetics and clinical effects. J Clin Oncol 2009; 27(35): 5972–5978
https://doi.org/10.1200/JCO.2008.20.4156 pmid: 19901119
36 Ramsey LB, Bruun GH, Yang W, Trevi?o LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui CH, Evans WE, Relling MV. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 2012; 22(1): 1–8
https://doi.org/10.1101/gr.129668.111 pmid: 22147369
37 Christian A. Fernandez, CA, Smith C, Yang W, Date M, Bashford D, Larsen E, Bowman WP, Liu C, Ramsey LB, Chang T, Turner V, Loh ML, Raetz EA, Winick NJ, Hunger SP, Carroll WL, Onengut-Gumuscu S, Chen WM, Concannon P, Rich SS, Scheet P, Jeha S, Pui CH, Evans WE, Devidas M, Relling MV. HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies. Blood 2014; 124(8): 1266–1276
https://doi.org/10.1182/blood-2014-03-563742 pmid: 24970932
38 Ramsey LB, Bruun GH, Yang W, Trevi?o LR, Vattathil S, Scheet P, Cheng C, Rosner GL, Giacomini KM, Fan Y, Sparreboom A, Mikkelsen TS, Corydon TJ, Pui CH, Evans WE, Relling MV. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 2012; 22(1): 1–8
https://doi.org/10.1101/gr.129668.111 pmid: 22147369
39 Ramsey LB, Panetta JC, Smith C, Yang W, Fan Y, Winick NJ, Martin PL, Cheng C, Devidas M, Pui CH, Evans WE, Hunger SP, Loh M, Relling MV. Genome-wide study of methotrexate clearance replicates SLCO1B1. Blood 2013; 121(6): 898–904
https://doi.org/10.1182/blood-2012-08-452839 pmid: 23233662
40 Stocco G, Yang W, Crews KR, Thierfelder WE, Decorti G, Londero M, Franca R, Rabusin M, Valsecchi MG, Pei D, Cheng C, Paugh SW, Ramsey LB, Diouf B, McCorkle JR, Jones TS, Pui CH, Relling MV, Evans WE. PACSIN2 polymorphism influences TPMT activity and mercaptopurine-related gastrointestinal toxicity. Hum Mol Genet 2012; 21(21): 4793–4804
https://doi.org/10.1093/hmg/dds302 pmid: 22846425
41 Jones TS, Kaste SC, Liu W, Cheng C, Yang W, Tantisira KG, Pui CH, Relling MV. CRHR1 polymorphisms predict bone density in survivors of acute lymphoblastic leukemia. J Clin Oncol 2008; 26(18): 3031–3037
https://doi.org/10.1200/JCO.2007.14.6399 pmid: 18565889
42 French D, Hamilton LH, Mattano LA Jr, Sather HN, Devidas M, Nachman JB, Relling MV; Children’s Oncology Group. A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Blood 2008; 111(9): 4496–4499
https://doi.org/10.1182/blood-2007-11-123885 pmid: 18285546
43 Wang X, Liu W, Sun CL, Armenian SH, Hakonarson H, Hageman L, Ding Y, Landier W, Blanco JG, Chen L, Qui?ones A, Ferguson D, Winick N, Ginsberg JP, Keller F, Neglia JP, Desai S, Sklar CA, Castellino SM, Cherrick I, Dreyer ZE, Hudson MM, Robison LL, Yasui Y, Relling MV, Bhatia S. Hyaluronan synthase 3 variant and anthracycline-related cardiomyopathy: a report from the children’s oncology group. J Clin Oncol 2014; 32(7): 647–653
https://doi.org/10.1200/JCO.2013.50.3557 pmid: 24470002
44 Diouf B, Crews K, Lew G, . Genome-Wide Association Analyses Identify Susceptibility Loci For Vincristine-Induced Peripheral Neuropathy In Children With Acute Lymphoblastic Leukemia. ASH 2013. Abstract 618
45 Dumitrescu L, Brown-Gentry K, Goodloe R, Glenn K, Yang W, Kornegay N, Pui CH, Relling MV, Crawford DC. Evidence for age as a modifier of genetic associations for lipid levels. Ann Hum Genet 2011; 75(5): 589–597
https://doi.org/10.1111/j.1469-1809.2011.00664.x pmid: 21777205
46 Kawedia JD, Liu C, Pei D, Cheng C, Fernandez CA, Howard SC, Campana D, Panetta JC, Bowman WP, Evans WE, Pui CH, Relling MV. Dexamethasone exposure and asparaginase antibodies affect relapse risk in acute lymphoblastic leukemia. Blood 2012; 119(7): 1658–1664
https://doi.org/10.1182/blood-2011-09-381731 pmid: 22117041
47 Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui CH, Evans WE. Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus. J Natl Cancer Inst 1999; 91(23): 2001–2008
https://doi.org/10.1093/jnci/91.23.2001 pmid: 10580024
48 Schmiegelow K, Al-Modhwahi I, Andersen MK, Behrendtz M, Forestier E, Hasle H, Heyman M, Kristinsson J, Nersting J, Nygaard R, Svendsen AL, Vettenranta K, Weinshilboum R; Nordic Society for Paediatric Haematology and Oncology. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study. Blood 2009; 113(24): 6077–6084
https://doi.org/10.1182/blood-2008-11-187880 pmid: 19224761
49 Relling MV, Gardner EE, Sandborn WJ, Schmiegelow K, Pui CH, Yee SW, Stein CM, Carrillo M, Evans WE, Klein TE; Clinical Pharmacogenetics Implementation Consortium. Clinical Pharmacogenetics Implementation Consortium guidelines for thiopurine methyltransferase genotype and thiopurine dosing. Clin Pharmacol Ther 2011; 89(3): 387–391
https://doi.org/10.1038/clpt.2010.320 pmid: 21270794
50 Yang SK, Hong M, Baek J, Choi H, Zhao W, Jung Y, Haritunians T, Ye BD, Kim KJ, Park SH, Park SK, Yang DH, Dubinsky M, Lee I, McGovern DP, Liu J, Song K. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet 2014; 46(9): 1017–1020
https://doi.org/10.1038/ng.3060 pmid: 25108385
51 Hoffman JM, Haidar CE, Wilkinson MR, Crews KR, Baker DK, Kornegay NM, Yang W, Pui CH, Reiss UM, Gaur AH, Howard SC, Evans WE, Broeckel U, Relling MV. PG4KDS: a model for the clinical implementation of pre-emptive pharmacogenetics. Am J Med Genet C Semin Med Genet 2014; 166C(1): 45–55
https://doi.org/10.1002/ajmg.c.31391 pmid: 24619595
52 Mullighan CG, Zhang J, Kasper LH, Lerach S, Payne-Turner D, Phillips LA, Heatley SL, Holmfeldt L, Collins-Underwood JR, Ma J, Buetow KH, Pui CH, Baker SD, Brindle PK, Downing JR. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 2011; 471(7337): 235–239
https://doi.org/10.1038/nature09727 pmid: 21390130
53 Shapiro E, Biezuner T, Linnarsson S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat Rev Genet 2013; 14(9): 618–630
https://doi.org/10.1038/nrg3542 pmid: 23897237
54 Perez-Garcia A, Ambesi-Impiombato A, Hadler M, Rigo I, LeDuc CA, Kelly K, Jalas C, Paietta E, Racevskis J, Rowe JM, Tallman MS, Paganin M, Basso G, Tong W, Chung WK, Ferrando AA. Genetic loss of SH2B3 in acute lymphoblastic leukemia. Blood 2013; 122(14): 2425–2432
https://doi.org/10.1182/blood-2013-05-500850 pmid: 23908464
55 Figueroa ME, Chen SC, Andersson AK, Phillips LA, Li Y, Sotzen J, Kundu M, Downing JR, Melnick A, Mullighan CG. Integrated genetic and epigenetic analysis of childhood acute lymphoblastic leukemia. J Clin Invest 2013; 123(7): 3099–3111
https://doi.org/10.1172/JCI66203 pmid: 23921123
56 Huether R, Dong L, Chen X, Wu G, Parker M, Wei L, Ma J, Edmonson MN, Hedlund EK, Rusch MC, Shurtleff SA, Mulder HL, Boggs K, Vadordaria B, Cheng J, Yergeau D, Song G, Becksfort J, Lemmon G, Weber C, Cai Z, Dang J, Walsh M, Gedman AL, Faber Z, Easton J, Gruber T, Kriwacki RW, Partridge JF, Ding L, Wilson RK, Mardis ER, Mullighan CG, Gilbertson RJ, Baker SJ, Zambetti G, Ellison DW, Zhang J, Downing JR. The landscape of somatic mutations in epigenetic regulators across 1,000 paediatric cancer genomes. Nat Commun 2014; 5: 3630
https://doi.org/10.1038/ncomms4630 pmid: 24710217
57 Hogan LE, Meyer JA, Yang J, Wang J, Wong N, Yang W, Condos G, Hunger SP, Raetz E, Saffery R, Relling MV, Bhojwani D, Morrison DJ, Carroll WL. Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies. Blood 2011; 118(19): 5218–5226
https://doi.org/10.1182/blood-2011-04-345595 pmid: 21921043
58 Bhatla T, Wang J, Morrison DJ, Raetz EA, Burke MJ, Brown P, Carroll WL. Epigenetic reprogramming reverses the relapse-specific gene expression signature and restores chemosensitivity in childhood B-lymphoblastic leukemia.. Blood 2012; 119(22): 5201–5210
https://doi.org/doi:10.1182/blood-2012-01-401687 pmid: 22496163
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