DNMT3A mutation analysis in adult patients with acute lymphoblastic leukemia

Ya-nan Liu , Na Zhang , Ying Wu , Li Yang , Xiao-yi Ding , Jian-feng Zhou , Min Xiao

Current Medical Science ›› 2015, Vol. 35 ›› Issue (3) : 337 -342.

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Current Medical Science ›› 2015, Vol. 35 ›› Issue (3) : 337 -342. DOI: 10.1007/s11596-015-1434-1
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DNMT3A mutation analysis in adult patients with acute lymphoblastic leukemia

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Abstract

DNA methyl-transferase 3A (DNMT3A) mutation has recently been identified as an independent risk factor for patients with acute myeloid leukemia (AML). However, reports are scanty on its rate and subsequent impact on patients with acute lymphoblastic leukemia (ALL), especially in Chinese population. In this study, we investigated the incidence and prognostic implication of DNMT3A mutation in 57 Chinese adult ALL patients. A total of 3 (5.3%) T-ALL cases were found to have the DNMT3A R882H mutation, which was significantly greater than that found in B-ALL subtype (P=0.048). The patients aged between 40 and 60 years old had higher mutation rate than other age groups (P=0.042). Patients with DNMT3A mutation had shorter overall survival (OS) than their wild-type counterparts. Our study demonstrated that Chinese ALL patients might develop DNMT3A mutation, which exerts a negative impact on their prognosis. These findings might help in risk stratification and treatment choice for Chinese ALL patients.

Keywords

DNMT3A mutation / acute lymphoblastic leukemia / overall survival

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Ya-nan Liu, Na Zhang, Ying Wu, Li Yang, Xiao-yi Ding, Jian-feng Zhou, Min Xiao. DNMT3A mutation analysis in adult patients with acute lymphoblastic leukemia. Current Medical Science, 2015, 35(3): 337-342 DOI:10.1007/s11596-015-1434-1

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References

[1]

ChengX, BlumenthalRM. Mammalian DNA methyltransferases: a structural perspective. Structure, 2008, 16(3): 341-350 PMCID: 2597194 PMID: 18334209

[2]

Rodriguez-OsorioN, WangH, RupinskiJ, et al. . Comparative functional genomics of mammalian DNA methyltransferases. Reprod Biomed Online, 2010, 20(2): 243-255 PMID: 20113962

[3]

HermannA, GowherH, JeltschA. Biochemistry and biology of mammalian DNA methyltransferases. Cell Mol Life Sci, 2004, 61(19–20): 2571-2587 PMID: 15526163

[4]

JurkowskaRZ, JurkowskiTP, JeltschA. Structure and function of mammalian DNA methyltransferases. Chembiochem, 2011, 12(2): 206-222 PMID: 21243710

[5]

Turek-PlewaJ, JagodzinskiPP. The role of mammalian DNA methyltransferases in the regulation of gene expression. Cell Mol Biol Lett, 2005, 10(4): 631-647 PMID: 16341272

[6]

YanXJ, XuJ, GuZH, et al. . Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet, 2011, 43(4): 309-315 PMID: 21399634

[7]

LeyTJ, DingL, WalterMJ, et al. . DNMT3A mutations in acute myeloid leukemia. N Engl J Med, 2010, 363(25): 2424-2433 PMCID: 3201818 PMID: 21067377

[8]

MarcucciG, MetzelerKH, SchwindS, et al. . Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia. J Clin Oncol, 2012, 30(7): 742-750 PMCID: 3295550 PMID: 22291079

[9]

LinJ, YaoDM, QianJ, et al. . Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome. PLoS One, 2011, 6(10): e26906 PMCID: 3204995 PMID: 22066015

[10]

TholF, WinschelC, LudekingA, et al. . Rare occurrence of DNMT3A mutations in myelodysplastic syndromes. Haematologica, 2011, 96(12): 1870-1873 PMCID: 3232272 PMID: 21880636

[11]

WalterMJ, DingL, ShenD, et al. . Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia, 2011, 25(7): 1153-1158 PMCID: 3202965 PMID: 21415852

[12]

Abdel-WahabO, PardananiA, RampalR, et al. . DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia, 2011, 25(7): 1219-1220 PMID: 21519343

[13]

BrecquevilleM, ReyJ, BertucciF, et al. . Mutation analysis of ASXL1, CBL, DNMT3A, IDH1, IDH2, JAK2, MPL, NF1, SF3B1, SUZ12, and TET2 in myeloproliferative neoplasms. Genes Chromosomes Cancer, 2012, 51(8): 743-755 PMID: 22489043

[14]

RaoN, ButcherCM, LewisID, et al. . Clonal and lineage analysis of somatic DNMT3A and JAK2 mutations in a chronic phase polycythemia vera patient. Br J Haematol, 2012, 156(2): 268-270 PMID: 21859430

[15]

JankowskaAM, MakishimaH, TiuRV, et al. . Mutational spectrum analysis of chronic myelomonocytic leukemia includes genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A. Blood, 2011, 118(14): 3932-3941 PMCID: 3193268 PMID: 21828135

[16]

CouronneL, BastardC, BernardOA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med, 2012, 366(1): 95-96 PMID: 22216861

[17]

GrossmannV, HaferlachC, WeissmannS, et al. . The molecular profile of adult T-cell acute lymphoblastic leukemia: Mutations in RUNX1 and DNMT3A are associated with poor prognosis in T-ALL. Genes Chromosomes Cancer, 2013, 52(4): 410-422 PMID: 23341344

[18]

NeumannM, HeeschS, SchleeC, et al. . Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutations. Blood, 2013, 121(23): 4749-4752 PMID: 23603912

[19]

RollerA, GrossmannV, BacherU, et al. . Landmark analysis of DNMT3A mutations in hematological malignancies. Leukemia, 2013, 27(7): 1573-1578 PMID: 23519389

[20]

Van VlierbergheP, Ambesi-ImpiombatoA, De KeersmaeckerK, et al. . Prognostic relevance of integrated genetic profiling in adult T-cell acute lymphoblastic leukemia. Blood, 2013, 122(1): 74-82 PMCID: 3701905 PMID: 23687089

[21]

ShivarovV, GueorguievaR, StoimenovA, et al. . DNMT3A mutation is a poor prognosis biomarker in AML: Results of a meta-analysis of 4500 AML patients. Leuk Res, 2013, 37(11): 1445-1450 PMID: 23962568

[22]

KimMS, KimYR, YooNJ, et al. . Mutational analysis of DNMT3A gene in acute leukemias and common solid cancers. APMIS, 2013, 121(2): 85-94 PMID: 23031157

[23]

NeumannM, GreifPA, BaldusCD. Mutational landscape of adult ETP-ALL. Oncotarget, 2013, 4(7): 954-955 PMCID: 3759672 PMID: 23807759

[24]

CornellRF, PalmerJ. Adult acute leukemia. Dis Mon, 2012, 58(4): 219-238 PMID: 22449370

[25]

IacobucciI, PapayannidisC, LonettiA, et al. . Cytogenetic and molecular predictors of outcome in acute lymphocytic leukemia: recent developments. Curr Hematol Malig Rep, 2012, 7(2): 133-143 PMCID: 3342501 PMID: 22528731

[26]

ShlushLI, ZandiS, MitchellA, et al. . Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature, 2014, 506(7488): 328-333 PMID: 24522528

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