Laboratory Assays in Patients with Acute Promyelocytic Leukemia and FLT3-TKD Mutations

Abstract

Acute Promyelocytic Leukemia (APL) is a well-characterized subtype of Acute Myeloid Leukemia (AML). The majority of patients with acute promyelocytic leukemia harbor the reciprocal translocation of t(15;17)(PML-RARα). Recent studies have shown that FMS-Like tyrosine kinase receptor-3 (FLT-3) mutations occur in approximately onethird of AML patients. Two major categories of clinically significant FLT3 activating mutations have been identified: Internal tandem duplication (ITD) mutations within the juxtamembrane domain of FLT-3 gene and missense point mutations in the tyrosine kinase domai. Several studies have demonstrated a poor overall survival with FLT-3 ITD mutation which is found in approximately 20-40% of AML patients. In contrast, the prognostic significance of FLT-3 TKD alone is still unclear, but some studies indicate that it also confers a poor prognosis in AML patients. The current study was performed on 66 [Male: 27(41%); Female: 39(59%)] APL patients to analyze and compare hematological parameters between APL patients with wild-type FLT-3(FLT3-WT) [87% (n=58)] and APL patients with mutant FLT3- TKD [12% (n=8)]. Quantification of PML-RARα transcripts was performed by Real-time quantitative PCR. FLT3-TKD mutation was detected by Polyacrylamide Gel Electrophoresis and CBC values were measured with a SYSMEX automated hematology analyzer. The participants of both cohorts were stratified into high-risk and low-risk groups based on their hematological parameters. The findings indicated that APL patients with FLT-3 TKD mutation had laboratory features with more favorable outcome compared with patients with wild-type FLT-3.