ISSN 2997-1036
International Journal of Hematology | Vol. 12, No. 2, February 2021 | pp. 9–16
DOI: 10.46882/2021/IJH/000132
Original Article
Title: Prevalence and molecular profiles of DNMT3A and IDH2 somatic mutations in adult acute myeloid leukemia variants
Names of Authors: G. M. Babalola¹, I. N. Nwosu², K. S. Abubakar³
Authors’ Affiliations: ¹Department of Haematology and Blood Transfusion, Lagos University Teaching Hospital, Lagos, Nigeria; ²Department of Medicine, University of Nigeria, Nsukka, Nigeria; ³Department of Pathology, Bayero University, Kano, Nigeria
Abstract: Epigenetic dysregulation driven by specific somatic mutations plays a major role in blocking differentiation in acute myeloid leukemia cells. This cross-sectional study investigated the mutational prevalence and clinical phenotypes of DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase 2 (IDH2) gene variations in 64 adult patients with newly diagnosed acute myeloid leukemia. Genomic DNA was isolated from peripheral blood leucocytes, followed by target-enrichment polymerase chain reaction and Sanger sequencing. DNMT3A mutations (predominantly R882) were detected in 25.0% (16 of 64) of the patients, while IDH2 mutations (R140 and R172 variants) occurred in 15.6% (10 of 64). Co-existing mutations in both genes were documented in 6.2% of the cases. Clinical correlation models revealed that patients harboring DNMT3A mutations displayed significantly higher baseline white blood cell counts and an increased prevalence of monocytic differentiation (FAB M4/M5 subtypes) compared to wild-type cohorts (P < 0.05). Conversely, isolated IDH2 mutations correlated with intermediate-risk cytogenetics and normal karyotypes. Screening for these somatic variants provides vital prognostic refinement, helping separate molecularly distinct myeloid sub-clones before initiating targeted differentiation therapies.
Keywords: Acute myeloid leukemia, DNMT3A mutation, IDH2 mutation, DNA methylation, molecular staging
Manuscript Timeline: Received: November 05, 2020; Revised: December 14, 2020; Accepted: January 10, 2020; Published: February 18, 2021