Clinical implication and prognostic significance of FLT3-ITD and ASXL1 mutations in Egyptian AML patients: A singlecenter study.

Abstract

BACKGROUND\nBoth of Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and Additional Sex Comb-like 1 (ASXL1) mutations are frequent and early genetic alteration events in acute myeloid leukemia (AML) patients. These genetic alterations may be associated with unfavorable prognosis.\n\n\nOBJECTIVE\nUp to our knowledge, this is the first study performed to evaluate the clinical implication and prognostic significance of FLT3-ITD and ASXL1 mutations and their coexistence on the outcome of Egyptian AML patients.\n\n\nMETHODS\nOur study included 83 patients with AML who were subjected to immunophenotyping and detection of FLT3-ITD and ASXL1 gene mutation by polymerase chain reaction (PCR) and real-time PCR, respectively.\n\n\nRESULTS\nFLT3-ITD and ASXL1 mutations were detected in 20.5% and 18.1% of AML patients respectively. Seven patients (8.4%) had co-expression of both genes mutation. FLT3-ITD mutation was significantly higher in younger age, higher WBCs count and poor cytogenetic risk patients (P= 0.01, < 0.001 and 0.008 respectively). ASXL1 mutation was significantly higher in intermediate cytogenetic risk patients (P= 0.2). The mean period of survival and relapse free survival (RFS) were significantly reduced in FLT3-ITD and ASXL1 mutations compared with their non-mutant types (P= 0.01 and 0.03 respectively). Both mutations were independent risk factors for overall survival (OS) and (RFS) in univariate and multivariate analysis in AML patients.\n\n\nCONCLUSION\nFLT3-ITD and ASXL1 gene mutations or their coexistence can predict a poor prognosis in AML patients.