DNMT3A Gene Polymorphismin Iraqi Acute Myeloid Leukemia Patients and its Relation to Prognostic Factors and Response to Therapy

Abstract

Acute myeloid leukemia (AML) is a complex and heterogeneous malignant disease of hematopoietic stem and progenitor cells characterized by the accumulation of immature blasts cells in the bone marrow, blood or other organs, that is related to  environmental, genetic and epigenetic factors. Previous studies have shown that single nucleotide polymorphisms (SNP) of DNMT3A  were correlated with the susceptibility of cancer, also suggested to play a crucial role in human cancer prognosis. The aim of the study is to assess the frequency of DNMT3A gene single nucleotide polymorphism (rs11695471) in Iraqi acute myeloid leukemia patients and it is association with disease development and response to treatment. The study included 80 persons, 40 AML patients and 40 healthy control age and sex matched. Routine investigations were collected which including symptoms and signs, physical examination, complete blood count, peripheral blood smears, bone marrow aspirates and immunophenotyping. RT (real time) polymerase chain reaction technique was used to detect DNMT3A gene polymorphism with Sa-cycler-96 well using genomic DNA isolated from peripheral blood and Taq Man SNP genotyping assay (rs11695471) for both patients and control. DNMT3A SNP rs11695471 was detected in all AML patients with 50% showing wild homozygous genotype and 50% showing the variant genotype, while 67.5% of control showing the wild homozygous genotype and 32.5% showed the variant genotype (P value=0.02). 77% of remission in AML cases are related to wild homozygous genotype (TT) of DNMT3A gene polymorphism, while 63% of non remission cases are related to the variant genotype(TA and AA). DNMT3A SNP rs11695471 is common among Iraqi AML patients and may force a high risk of AML development and influence response to treatment.