Evaluation of Cytogenetic Changes and FLT3 mutations in Patients with Acute Promyelocytic Leukemia

The secondary genetic changes other than the PML-RARA fusion gene may contribute to the acute promyelocytic leukemogenesis. Chromosomal alterations and mutation of FLT3 tyrosine kinase receptor gene are the frequent genetic alterations in acute myeloid leukemia (AML). However, the prognostic significance of FLT3 mutations in acute promyelocytic leukemia (APL) is not firmly established.Methods and materials: Cytogenetic analysis of 45 APL patient's BM samples, FLT3 ITD screening by fragment length analysis and FLT3 D835 mutation by melting curve analysis in 23 APL samples was screened in this study. Cytogenetic study showed 14.3% trisomy 8 and 17.1% chromosomal abnormalities other than t(15;17). About13% of the patients had FLT3 internal tandem duplications (ITDs), and 26% had D835 point mutation. FLT3 ITD mutation was associated with higher white blood cell (WBC) count at presentation and poor prognosis. As the PML-RARA is not sufficient to develop APL, we assume FLT3 mutations and additional chromosomal alterations we found in this APL series may cooperate with PML-RARA in APL development.