DNMT3A mutations in acute myeloid leukemia: Stability during disease evolution and clinical implications
Journal
Blood
Journal Volume
119
Journal Issue
2
Pages
559-568
Date Issued
2012
Author(s)
Kuo Y.-Y.
Liu C.-Y.
Lee M.C.
Tseng M.-H.
Huang C.-F.
Chiang Y.-C.
Lee F.-Y.
Liu M.-C.
Liu C.-W.
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 the present study of 500 patients with de novo AML, DNMT3A mutations were identified in 14% of total patients and in 22.9% of AML patients with normal karyotype. DNMT3A mutations were positively associated with older age, higher WBC and platelet counts, intermediate- risk and normal cytogenetics, FLT3 internal tandem duplication, and NPM1, PTPN11, and IDH2 mutations, but were negatively associated with CEBPA mutations. Multivariate analysis demonstrated that the DNMT3A mutation was an independent poor prognostic factor for over-all survival and relapse-free survival in total patients and also in normokaryotype group. A scoring system incorporating the DNMT3A mutation and 8 other prognostic factors, including age, WBC count, cytogenetics, and gene mutations, into survival analysis was very useful in stratifying AML patients into different prognostic groups (P < .001). Sequential study of 138 patients during the clinical course showed that DNMT3A mutations were stable during AML evolution. In conclusion, DNMT3A mutations are associated with distinct clinical and biologic features and poor prognosis in de novo AML patients. Furthermore, the DNMT3A mutation may be a potential biomarker for monitoring of minimal residual disease. ? 2012 by The American Society of Hematology.
SDGs
Other Subjects
CD135 antigen; cytarabine; DNA methyltransferase 3A; idarubicin; mitoxantrone; nucleophosmin; protein tyrosine phosphatase SHP 2; acute granulocytic leukemia; adult; age; aged; article; cancer combination chemotherapy; cancer risk; cancer survival; cytogenetics; disease course; drug megadose; female; gene duplication; gene mutation; gene sequence; genetic analysis; hematopoietic stem cell transplantation; human; karyotype; leukocyte count; major clinical study; male; overall survival; priority journal; prognosis; recurrence free survival; thrombocyte count
Type
journal article