Mutational screening of RTK-BRAF genes in de novo adult acute myeloid leukemia

Background: Acute myeloid leukemia (AML) is derived from primitive hematopoietic stem cells or progenitor cells due to genetic variations such as chromosomal abnormalities and molecular alterations. Mutations in the RTK-BRAF genes are involved in leukaemogenesis. Few reports simultaneously concerning the mutation alteration of the RTK-BRAF genes have been publicized in AML subjects. The current study aimed to screen the mutations of RTK-BRAF genes in Iranian de novo adult AML subjects. Methods: Mutations of RTK-BRAF genes were investigated in bone marrow specimens from 58 patients with de novo adult AML. High-Resolution Melt (HRM) curve analysis was performed for the identification of FLT3-ITD and D835 mutations. Mutations in the NPM1 (exon12), BRAF (exons11 and 15), PTPN11(exons 3 and 13) and cFMS (exon22) were detected using Sanger sequencing method. Results: Totally, FLT3 and NPM1 mutations were found in 34.48% and 25.86% of AML patients, respectively. Moreover, mutations in the FLT3 and NPM1 genes were significantly higher in normal karyotype AML subjects (52.38% and 38%, respectively) than patients with abnormal karyotype (p-value = 0.001 and p-value = 0.002, respectively). No mutations were detected in other RTK-BRAF genes. Conclusion: According to the findings of this research, in addition to the chromosomal abnormalities in the patients with acute myeloid leukemia, FLT3 and NPM1 mutations were the most recurrent genetic alterations. Identification of these alterations may help to choose appropriate treatment and improve the patients' outcome.