A Mutational and Expressional Analysis of Dnmt3a in Acute Myeloid Leukemia Cytogenetic Subgroups Publisher Pubmed



Zareabdollahi D¹ ; Safari S¹ ; Movafagh A¹ ; Riaziisfahani S² ; Ghadyani M³ ; Hashemigorji F⁴ ; Nasrollahi MF⁵ ; Omrani MD¹ Show Affiliations
Source: Hematology Published:2015

Abstract

Objectives: Despite numerous studies in order to determine the allele frequency and clinical impact of DNA methyltransferase 3 A (DNMT3A) gene mutations in acute myeloid leukemia (AML), reports about the expression analysis of this gene are rare and between the available, differences are evident. Methods: In this study, we decided to investigate DNMT3A possible expression changes with regard to their mutation and cytogenetic status in a series of 96 AML patients. Results: Mutations were founded in 17 of the 96 patients (17.7%) and associated with higher age and white blood cell count (P < 0.001). Our mutants have had shorter overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P = 0.011) than those without. Multivariate analysis showed that DNMT3A mutation is an independent prognostic indicator for OS and RFS (P < 0.001). In relation to expression results, we had over and under expression for our favorable and unfavorable cytogenetic subgroups, respectively (P = 0.005 and P < 0.001, respectively). In intermediate subgroup, total DNMT3A expression did not alter (P = 0.575). Interestingly, we noticed similar expression results for DNMT3A transcript 2, to that of the total. Discussion and conclusion: In relation to DNMT3A expression, from the perspective of diagnostic application and its biological significance, it is difficult to accept its primacy over cytogenetic value in favorable and unfavorable subgroups and if so, we did not address this issue in our study due to sample size limitation. In intermediate subgroup, particularly in normal karyotype-AML, given the lack of convincing results, it seems unlikely that DNMT3A expression analysis could attract attention in diagnostic workup and risk prediction of AML. © W.S. Maney & Son Ltd 2015.