| Title: |
DNMT3A mutations in acute myeloid leukemia: stability during disease evolution and clinical implications. |
| Authors: |
Hsin-An Hou1,2, Yuan-Yeh Kuo3, Chieh-Yu Liu4, Wen-Chien Chou1,5, Ming Cheng Lee1, Chien-Yuan Chen1, Liang-In Lin6, Mei-Hsuan Tseng1, Chi-Fei Huang1, Ying-Chieh Chiang1, Fen-Yu Lee7, Ming-Chih Liu7, Chia-Wen Liu7, Jih-Luh Tang1, Ming Yao1, Shang-Yi Huang1, Bor-Sheng Ko1, Szu-Chun Hsu5, Shang-Ju Wu1, Woei Tsay1 |
| Source: |
Blood. 1/12/2012, Vol. 119 Issue 2, p559-568. 10p. |
| Subject Terms: |
*ACUTE myeloid leukemia, *CYTOGENETICS, *GENETIC mutation, *MULTIVARIATE analysis, *LEUKOCYTES, *BLOOD platelets |
| Abstract: |
DNMT3A mutations are associated with poor prognosis in acute myeloid leukemia (AML), but the stability of this mutation during the clinical course remains unclear. In this study, among 500 patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and 22.9% of patients with normal karyotype (CN-AML). DNMT3A mutations were closely associated with older age, higher white blood cell (WBC) and platelet counts, intermediate-risk and normal cytogenetics, FLT3-ITD, and mutations of NPM1, PTPN11 and IDH2, but negatively associated with CEBPA mutation. Multivariate analysis demonstrated that DNMT3A mutation was an independent poor prognostic factor for overall survival and relapse-free survival among total patients and CN-AML group. A scoring system incorporating DNMT3A mutation and eight other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was proved to be very useful to stratify AML patients into different prognostic groups (P<0.001). Sequential study in 138 patients during the clinical course showed that DNMT3A mutations were quite stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biological features and poor prognosis in de novo AML patients. Furthermore, the mutation may be a potential biomarker for monitoring of minimal residual disease. [ABSTRACT FROM AUTHOR] |
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