Acute myeloid leukemia (AML) is a complex and heterogeneous hematopoietic tissue neoplasm. Several molecular markers have been described that help to classify AML patients into risk groups. DNA methyltransferase 3A (DNMT3A) gene mutations have been recently identified in about 22% of AML patients and associated with poor prognosis as an independent risk factor. Our aims were to determine the frequency of somatic mutations in the gene DNMT3A and major chromosomal translocations in a sample of patients with AML. We investigated in 82 samples of bone marrow from patients with AML for somatic mutations in DNMT3A gene by sequencing and sought major fusion transcripts by RT-PCR. We found mutations in the DNMT3A gene in 6 patients (8%); 3 were type R882H. We found fusion transcripts in 19 patients, namely, AML1/ETO ( ; 6.1%), PML/RARα ( ; 14.6%), MLL/AF9 (0; 0%), and CBFβ/MYH11 ( ; 2.4%). The identification of recurrent mutations in the DNMT3A gene and their possible prognostic implications can be a valuable tool for making treatment decisions. This is the first study on the presence of somatic mutations of the DNMT3A gene in patients with AML in Brazil. The frequency of these mutations suggests a possible ethnogeographic variation. 1. Introduction Acute myeloid leukemia (AML) is a complex and heterogeneous hematopoietic tissue neoplasm caused by gene mutations, chromosomal rearrangements, deregulation of gene expression, and epigenetic modifications. These changes lead to unregulated proliferation and loss of differentiation capacity of myeloid hematopoietic cells. In recent years, several important prognostic molecular markers have been described for AML which not only improved disease characterization, but also allowed stratification of patients into risk groups and can guide therapeutic decision-making [1]. However, these molecular markers are often unable to provide accurate prognostic and therapeutic information, since the course of the disease varies significantly between patients belonging to the same risk category [2–4]. The traditional view of cancer as a disease caused by some genetic mutation has been replaced by the concept of a complex network of gene deregulation and epigenetic changes. Additionally, although extremely important, those mutations that have been reported are found in only a minority of patients with AML [5–7]. The distinct components of epigenetic machinery such as DNA methylation, covalent modifications of histones, and noncoding RNAs have been described as cocontrollers of gene expression and within a context of cancer may
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