A mutational and expressional analysis of DNMT3A in acute myeloid leukemia cytogenetic subgroups

• Published in: Hematology (Luxembourg) Vol. 20; no. 7; pp. 397 - 404
• Main Authors: Zare-Abdollahi, Davood, Safari, Shamsi, Movafagh, Abolfazl, Riazi-Isfahani, Sahand, Ghadyani, Mojtaba, Feyzollah, Hashemi-Gorji, Nasrollahi, Mohammad Foad, Omrani, Mir Davood
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.08.2015
• Subjects: Acute myeloid leukemia; Adolescent; Adult; Age Factors; AML; Disease-Free Survival; DNA (Cytosine-5-)-Methyltransferases - biosynthesis; DNA (Cytosine-5-)-Methyltransferases - genetics; DNMT3A; Expression; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute - enzymology; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - mortality; Leukocyte Count; Male; Middle Aged; Mutation; Outcome; Survival Rate; AML; Mutation; Expression; Acute myeloid leukemia; Outcome; DNMT3A
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1179/1607845415Y.0000000001

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.