Gene expression profiling of the DNMT3A R882 mutation in acute leukemia

Huang,Xiangnan; Ma,Daoxin; Dong,Wenhao; Li,Peng; Lu,Ting; He,Na; Tian,Tian; Liu,Na; Du,Yahui; Ji,Chunyan

doi:10.3892/ol.2013.1347

Gene expression profiling of the DNMT3A R882 mutation in acute leukemia

Authors:
- Xiangnan Huang
- Daoxin Ma
- Wenhao Dong
- Peng Li
- Ting Lu
- Na He
- Tian Tian
- Na Liu
- Yahui Du
- Chunyan Ji
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Affiliations: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
Published online on: May 14, 2013 https://doi.org/10.3892/ol.2013.1347
Pages: 268-274

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Abstract

DNA methyltransferase 3A (DNMT3A) is one of two human de novo DNA methyltransferases essential for the regulation of gene expression. DNMT3A mutations and deletions have been previously observed in acute myeloid leukemia (AML), myelodysplastic sydromes and myeloproliferative neoplasms. However, the involvement of DNMT3A in acute lymphoblastic leukemia (ALL) has rarely been reported. In the present study, PCR and direct sequencing was performed to analyze mutations of DNMT3A amino acid residue 882 in 99 acute leukemia patients, including 57 AML patients, 41 ALL patients and a single biphenotypic acute leukemia (BAL) patient. DNMT3A expression was detected in mononuclear cells of the bone marrow in these patients and in normal individuals using real‑time quantitative polymerase chain reaction, and 17.5% (10/57) of AML patients were found to exhibit DNMT3A mutations. Four missense mutations were observed in the DNMT3A‑mutated AML patients, including R882 mutations and a novel single nucleotide polymorphism resulting in the M880V amino acid substitution. However, the ALL and BAL patients were not found to exhibit DNMT3A mutations. The DNMT3A expression levels in the AML patients were significantly higher compared with those of the ALL patients or normal controls. The reduced expression levels of DNMT3A were associated with a significantly lower complete remission rate in the AML patients. However, in the ALL patients, no statistical significance was identified. The results of the present study indicate that DNMT3A may play varying roles in the regulation of DNA methylation in AML and ALL.

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