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Objectives: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for undertaking the current study.Methods: The prevalence and the potential prognostic impact of FLT3 mutations in 39 acute myeloid leukemia patients were analyzed by genomic polymerase chain reaction. Twelve samples with FLT3/ITDs and 27 acute myeloid leukemia samples without the mutations were compared with respect to clinical prognosis and FAB subtype. Results were correlated with cytogenetic data and the clinical response.Results: FLT3/ITD mutations were found in 31% of patients. FLT3/ITD was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype (83%). Interestingly, half of the FLT3/ITD aberrations were found in patients with FAB M1 (50%), and fewer were found in patients with FAB M2 (8%), M4 (8%), and M5 (8%). Although less frequent in patients with cytogenetic aberrations, FLT3/ITDs were found in 17% of patients with t(15;17). Although the study was powered to 80%, patients with FLT3/ITD mutation did not show shorter complete remission duration or a higher relapse rate.Conclusion: The data confirm that FLT3/ITD mutations represent a common alteration in adult acute myeloid leukemia, mainly with normal karyotype (83%) and de novo acute myeloid leukemia (75%), as compared to secondary acute myeloid leukemia (25%) (p

Background and Aim: FLT3 gene is a member of class III receptor Tyrosine Kinase, which is expressed in most patients with acute myeloid leukemia (AML). Mutations of FLT3 such as Internal Tandem Duplication (ITD) and point mutation of the D835 are the most common genetic defects in myeloid leukemia. These two mutations in patients with MLA and their effect on survival rate were studied for the first time in Iran. Materials and Methods: DNA was extracted from the blood or bone marrow samples of 100 patients with AML from October 2008 to September 2009. For further analysis, PCR was performed to determine the prevalence of these mutations and their association with prognosis. Moreover, t and x2 statistical tests were applied for data analysis. Results: According to the results, 15% of patients revealed FLT3-ITD mutations and 8% showed mutation of D835 in FLT3 gene. In terms of achieving complete remission (CR), patients with mutation of ITD had more chance than those without such mutation (83.5% versus 53.3%). The white blood cell count was significantly higher in the ITD+ (mean = 73,646/ml) than ITD- patients (mean = 26,580/ml). Conclusion : The results indicate that FLT3-ITD mutations may reduce the chances of Complete Remission (CR) in patients; however, FLT3-ITD mutation is an important factor in selecting appropriate treatment.

Background and Aim: FLT3 gene is a member of class III receptor Tyrosine Kinase, which is expressed in most patients with acute myeloid leukemia (AML). Mutations of FLT3 such as Internal Tandem Duplication (ITD) and point mutation of the D835 are the most common genetic defects in myeloid leukemia. These two mutations in patients with MLA and their effect on survival rate were studied for the first time in Iran. Materials and Methods: DNA was extracted from the blood or bone marrow samples of 100 patients with AML from October 2008 to September 2009. For further analysis, PCR was performed to determine the prevalence of these mutations and their association with prognosis. Moreover, t and x2 statistical tests were applied for data analysis. Results: According to the results, 15% of patients revealed FLT3-ITD mutations and 8% showed mutation of D835 in FLT3 gene. In terms of achieving complete remission (CR), patients with mutation of ITD had more chance than those without such mutation (83.5% versus 53.3%). The white blood cell count was significantly higher in the ITD+ (mean = 73,646/ml) than ITD- patients (mean = 26,580/ml). Conclusion : The results indicate that FLT3-ITD mutations may reduce the chances of Complete Remission (CR) in patients however, FLT3-ITD mutation is an important factor in selecting appropriate treatment.

Background. FLT3 is a class III receptor tyrosine kinase expressed in normal stem cells and blasts of myeloid leukemia. Internal tandem duplication (ITD) of the FLT3 gene affecting the exons 14 and 15 leads to ligand-independent FLT3 dimerization and constitutive activation. This stimulates proliferation and induces inhibition of apoptosis which contributes to leukemogenesis. We have screened a panel of acute myeloid leukemia (AML) patients for the occurrence of FLT3/ITD mutation and correlated this mutation to patients’ survival and basic hematological parameters.Methods. RT-PCR for ITD in exons 14 and 15 of FLT3 gene was done on bone marrow samples of 67 AML patients at diagnosis.Results. There was a 16.4% incidence of FLT3/ITD mutation in the cohort of examined patients. By cytognetic subgroups there were 2/6 t(15;17) and 1 of 4 t(8;21) positive patients. The rest had normal and 2 had complex karyotype. Majority were of FAB M2 or M4 phenotype. For a subset of patients taken into comparative survival analysis there was a clear disadvantage for FLT3/ITD patients. No difference was found for basic hematological parameters between two groups.Conclusions. As it is evident today that FLT3/ITD is the single most common genetic abnormality in AML that also presents unfavorable clinical prognostic marker, it should be included in molecular diagnostic testing of acute myeloid leukemia.