Assessment of Association Between FLT3-ITD Gene Mutation and CD135 Expression and Their Correlation With Hematological,Immunophenotypic and Biochemical Characteristics in Acute Myeloid Leukemia.

Acute leukemias are clonal malignant diseases of immature hematopoietic system ,characterized by clonal evolution and considerable genetic, epigenetic, and phenotypic heterogeneity,and constitute a common cause of morbidity and mortality worldwide.[1] Gene expression profiling has improved the molecular classification and prognosis of Acute leukemias, where molecular testing has become mandatory for further classify into prognostic groups. Among the genetic aberrations, alterations of the FMS-like tyrosine kinase 3 (FLT3) gene. [2] FLT3 is a type 3 receptor tyrosine kinase that plays an important role in the expansion and proliferation of multi-potent progenitor cells within the bone marrow.[3] mutations of FLT3 induce a constitutional activation of tyrosine kinases and several downstream targets resulting in proliferation and growth of malignant cells ,myeloproliferative phenotype , high tumor burden,and a characteristic hematological , immunophenotypic and biochemical profile that can be identified during routine diagnostic workup.[4]Two mutations exist in these cells: FLT3-ITD (internal tandem duplication), and FLT3-TKD, a point mutation in the tyrosine kinase domain.[5] FLT3-ITD is a common driver mutation, seen with a frequency of 20 to 30% ,and significantly affecting the pathogenesis and the clinical outcome . Genetic testing for FLT3-ITD mutation at diagnosis is done to risk stratify patients and to guide therapeutic decisions.[6-8] FLT3 receptor/CD135 is a transmembrane tyrosine kinase receptor, normally expressed on the surface of hematopoietic stem cells and is lost upon cell differentiation , activation of the receptor resulting in stimulating survival and proliferation, and inhibiting apoptosis of progenitor cells . Overexpression of the FLT3 receptor has been reported to be associated with high risk for relapse in patients with acute leukemia .[2]