Abstract:

Objective To compare the expression difference of DNA methyltransferase（DNMT）3A between adult patients with de novo acute myeloid leukemia （AML） and healthy controls,and to investigate the relationships of DNMT3A expression with French-American-British（FAB）classification, nucleophosmin 1（NPM1）, FMS-like tyrosine kinase 3（FLT3） and c-KIT. Methods The expressions of DNMT3Awere determined by fluorescence quantitation polymerase chain reaction （PCR） in 78 de novo AML adult patients and 10 healthy controls. Results Compared with healthy control group,the expression ofDNMT3A decreased in de novo AML adult group （P=0.002）. There was a relationship between FAB classification and DNMT3A expression （r=0.342,P=0.002）. M3 and M5 patients showed significant difference in the expression of DNMT3A （P=0.001）. The expression of DNMT3A was significantly higher in NPM1 mutation patients than in non-NPM1 mutation patients （P=0.001）. The DNMT3Aexpression increased in NPM1⁺/FLT3-internal tandem duplication （ITD）^- patients compared with other patients （NPM1⁺/FLT3-ITD⁺,NPM1^-/FLT3-ITD⁺ and NPM1^-/FLT3-ITD^-） （P=0.007）. The expression of DNMT3A in patients with c-KIT mutation was lower significantly than that in patients without c-KIT mutation （P=0.007）. There was no correlation between DNMT3A expression and blast cell proportion in bone marrow smear （r=0.208,P=0.078）. There was no statistical significance for DNMT3A expression between patients with and without abnormal karyotype （P=0.214）. No statistical significance was found in DNMT3A expression between patients with and without FLT3 mutation （P=0.397）. Conclusions In adult patients with de novo AML,DNMT3A expression is down regulated and has difference with FAB classification. The low expression of DNMT3A may play an important role in the pathogenesis of AML by co-operating with NPM1 wild type and c-KIT mutation.

Key words: DNA methyltransferase 3A, Acute myeloid leukemia, Fluorescence quantitation polymerase chain reaction, Gene mutation