1556 Journal of Experimental Hematology 2011 19 6 1556-1560 Article ID 1009-2137 2011 06-1556 - 05 DNMT3A 361000 DNA AML DNA 3A DNMT3A DNA 20% 882 DNMT3A 60 AML-M 4 M 5 MDS PMF DNMT3A DNMT3A MRD DNMT3A DNMT3A DNA R733. 71 A DNMT3A Gene Mutations in Acute Myeloid Leukemia Review CHEN Ya-Mei LU Quan-Yi Department of Hematology Xiamen University Zhongshan Hospital Xiamen 361000 Fujian Province China Corresponding Author LU Quan-Yi Senior Physician Professor. Tel 0592 2292032. E-mail quanyilu@ hotmail. com Abstract Epigenetic changes including abnormal DNA methylation have been identified to play significant roles in tumor initiation and progression. Recently mutations of DNMT3A were identified in acute myeloid leukemia AML which possibly caused changes in DNA methylation and indicated a poor prognosis. Sequencing analysis showed that most of the mutations were single nucleotide variations including a hotspot Arg882. DNMT3A mutations were detected in about 20% AML patients and closely associated with the age over 60 the M 4 M 5 subtypes and intermediate-risk cytogenetics. Others showed that these alterations also present in myelodysplastic syndrome MDS and primary myelofibrosis PMF prior to development of the obvious leukemia indicating that these mutations might contribute to leukemogenesis. However its prognostic value of minimal residual disease and role of therapeutic targets are still unclear focusing on a large cohort of AML patients will solve these issues. In this review the achievement in studing DNMT3A gene mutation are summarized and the latest research progress is briefly discussed. Key words DNMT3A gene epigenetics DNA methylation acute myeloid leukemia J Exp Hematol 2011 19 6 1556-1560 acute myeloid leukemia AML NPM1 2 1. 62 /10 FLT3 3 CEBPA 4 IDH ASXL1 DNMT3A 5 6 DNMT3A DNA 3ADNA AML WHO. 0592 AML 40% 2292032. E-mail quanyilu@ hotmail. com AML NC-AML 1 2011-10 - 05 2011-10 - 17
DNMT3A 1557 14 DNMT3A CpG DNA DNA DNMT DNA DNA CpG DNA RNA DNA DNA DNA DNA 5 5 DNMT3A - - CpG CpG DNMT 2010 Yamashita 15 74 DNMT3A DNMT 2p23 3 4. 1% DNMT3A 882 DNA 109 615 bp ORF 4 314 bp DNA CDS 2 739 bp 912 50% Ley 6 DNMT1 DNMT2 DNMT3B AML DNMT3A DNMT3L DNMT 22% 1 33. 7% S- SAM 2 / 3 DNMT3A 3 882 7 3' 4 8 DNMT3A 3B N R882H R882C R882P PHD α / R882S X ARTX Otani 9 DNMT3A Yan 16 H3K4 AML-M 5 DNMT3A 20. 5% - AML-M 4 DNMT N C 882 13. 6% DNMT3A GK 10 882 - -DNA DNA DNMT3A Walter 17 8% 12 /150 3B MDS 882 DNA CpG Abdel-Wahab 18 DNMT1 DNMT3 7% 3 /46 AML Qiao 19 77 DNMT 11 AML 6 11. 9% DNMT3A DNMT3A DNMT3A2 882 1 874 12 DNA CEBPA DNMT3A CD4 /CD7 DNA DNMT3A 13 DNA
1558 J Exp Hematol 2011 19 6 DNMT3A 2 2 22 23 24 25 882 AML MDS 26 882 Blum 27 DNMT3A DNA AML DNA DNMT3A mrna DNMT3A Ley 6 Yan 16 AML-M 4 AML-M 5 DNMT3A AML-M 4 882 WHO t 15 17 t 8 21 inv 16 1 DNMT3A AML DNMT3A 2 20% 882 HSC HSC 20 882 DNA Ley 6 882 NPM1 FLT3 DNMT3A 882 - -DNA AML HSC DNMT3A DNMT3B Tadokoro 21 DNMT3A DNMT3B HSC HSC DNMT3A HSC 40% NC- DNMT3A AML NPM1 FLT3 CEBPA 1 DNMT3A NPM1 FLT3 CEBPA IDH1 IDH2 JAK2 Ley 6 33. 7% NC-AML TET2 ASXL1 NPM1 CEBPA DNMT3A NC-AML DNMT3A Ley 6 MLL RARα DNMT3A DNMT3A Walter 17 Abdel- AML Wahab 18 DNMT3A 30% - 50% RNA mir-29b DNMT3A AML MRD 28 29 DNMT3A DNMT Ley 6
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