Abstract
Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS.
Highlights
Tumorigenesis is known to be a multistep process, which is the result of genetic alterations and epigenetic changes [1]
Somatic mutations in DNMT3A gene have been found in acute myeloid leukaemia (AML) with a frequency of 22.1% [3]
Bone marrow specimens obtained at the time of complete hematologic remission from five AML patients with DNMT3A mutations at initial diagnosis and peripheral blood from 73 healthy individuals were used as control
Summary
Tumorigenesis is known to be a multistep process, which is the result of genetic alterations and epigenetic changes [1]. This work studied the occurrence of DNMT3A mutations in Chinese AML and MDS patients. Bone marrow specimens obtained at the time of complete hematologic remission from five AML patients with DNMT3A mutations at initial diagnosis and peripheral blood from 73 healthy individuals were used as control. In the cohort of 372 patients, 16 cases were discovered to harbor a heterozygous R882 mutation of DNMT3A, including R882H (n = 11), R882C (n = 4), and R882P (n = 1).
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