Cancer Cell International | |
DNMT3A mutations and clinical features in Chinese patients with acute myeloid leukemia | |
Zhipeng Li1  Hang Wang2  Yamei Chen1  Quanyi Lu1  | |
[1] Department of Haematology, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, 361004, China;Department of Biomedical Sciences and the Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, Fujian, China | |
关键词: Gene mutations; Acute myeloid leukemia; DNMT3A; | |
Others : 794547 DOI : 10.1186/1475-2867-13-1 |
|
received in 2012-09-24, accepted in 2013-01-08, 发布年份 2013 |
【 摘 要 】
Mutations in DNA methyltransferase 3A (DNMT3A) gene were recently demonstrated in acute myeloid leukemia(AML). Approximately 20% patients with AML carry DNMT3A gene mutations and was associated with a poor clinical outcome. but its clinical implications in Chinese AML patients are largely unknown. We analyzed 101 adult AML patients in china and found 14 patients (13.9%) harboring this mutation. 9 patient with M5, 2 patients with M1, 2patient with M2 and 1 patient with M3. We identified 11 missense mutation,2 nonsense and 30 bp deletion encompassing DNMT3A. The most common of them was predicted to affect 882Arg(in 4 patients). Double mutations were detected in two cases.10 of 33(43.5%). DNMT3A mutations occurred more frequently in older (age > 50y,p < 0.05) and the outcome is too badly for these patients. We concluded that DNMT3A mutations are highly recurrent in AML and is associated with distinct clinical and biologic characteristics and seems to be a useful as a prognostic marker.
【 授权许可】
2013 Lu et al.; licensee BioMed Central Ltd.
Files | Size | Format | View |
---|---|---|---|
Figure 1. | 50KB | Image | download |
Figure 2. | 53KB | Image | download |
Figure 1. | 90KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 1.
【 参考文献 】
- [1]Tara K, Gregory DW, Chen Y: Molecular prognostic markers for adult acute myeloid leukemia with normal cytogenetics. J Hematol Oncol 2009, 2:23. BioMed Central Full Text
- [2]Levis M, Small D: FLT3 ITDoes matter in leukemia. Leukemia 2003, 17:1738-1752.
- [3]Gilliland DG, Griffin JD: The roles of FLT3 in hematopoiesis and leukemia. Blood 2002, 100:1532-1542.
- [4]Tefferi A: Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010, 24(6):1128-38.
- [5]Yamashita Y, Yuan J, Suetake I: Array-based genomic resequencing of human leukemia. Oncogene 2010, 29:3723-3731.
- [6]Ley TJ, Ding L, Walter MJ: DNMT3A Mutations in Acute Myeloid Leukemia. N Engl J Med 2010, 363:2460-2461.
- [7]Yan XJ, Xu J, Gu ZH: Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet 2011, 13(4):309-315.
- [8]Tien HF, Wang CH, Lin MT: Correlation of cytogenetic results with immunophenotype, genetype, clinical features, and ras mutation in acute myeloid leukemia: a study of 235 Chinese patients in Taiwan. Cancer Genet Cytogenet 1995, 84:60-68.
- [9]Ewalt M, Galili NG, Mumtaz M: DNMT3A mutations in high-risk myelodysplastic syndrome parallel those found in acute myeloid leukemia. Blood Cancer J 2011, 1(3):e9.
- [10]Jaenisch R, Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 2003, 33:245-254.
- [11]Ling Y, Sankpal UT Robertson AK: Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription. Nucleic Acids Res 2004, 32:598-610.
- [12]Tang M, Xu W, Wang Q: DNMT and its Epigenetic Regulation for Lung Cancer Therapy. Curr Genomics 2009, 10:336-52.
- [13]Trowbridge JJ, Snow JW, Kim J: DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell 2009, 2(4):442-449.