Mutational Analysis of FLT3 Internal Tandem Duplication and D835 in De novo Adult Acute Myeloid Leukemia

Abstract

Aims: Acute myeloid leukemia is a clonal hematopoietic malignant disease, resulting from genetic alterations in normal hematopoietic stem cells. Advances in the genomics of acute myeloid leukemia have identified several recurrent gene mutations such as FLT3 that its mutations confer poor outcome to patients. The aim of the present study was to investigate the frequency of FLT3-ITD and FLT3-D835 mutations in Iranian de novo adult AML patients. Study Design: Cohort study. Place and Duration of Study: Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, between January 2016 to June 2017. Methodology: We performed mutational analysis in order to detect FLT3-ITD and FLT3-D835 mutations in a group of 91 de novo adult AML patients by using the conventional PCR and PCR-RFLP methods, respectively. Results: The results of the mutation analysis showed that in total 30.76 percent of patients had activating mutations of FLT3-ITD (27.47%) and FLT3-D835 (3.29%). Furthermore, a significant correlation was observed between with white blood cell (WBC) and blast cell count and the detected mutations (P-value<0.001). Except for the M6, FLT3 mutations were identified in other FAB type groups. In addition, FLT3-ITD and FLT3-D835 mutations were observed in all three cytogenetic risk groups, However, a significant correlation was detected between FLT3-ITD mutation and normal karyotype (P-value=0.032). Conclusion: Activating mutations in the FLT3 are recurrent in Iranian de novo adult AML patients. The mutational analysis of genes such as FLT3 in acute myeloid leukemia may be helpful in categorizing of the patients, determining prognosis and improving the treatment.