FLT3 Mutation as a Significant Prognostic Marker in de novo Acute Myeloid Leukemia Patients: Incidence, Distribution and Association with Cytogenetic Findings in a Study from South India

Background: fms-like tyrosine kinase 3 is a tyrosine kinase receptor that plays animportant role in proliferation and differentiation of hematopoietic stem cells. internaltandem duplication and tyrosine kinase domain mutation are the two most commontypes of fms-like tyrosine kinase 3 mutations frequently reported in acute myeloidleukemia associated with pathogenesis of this disease. the present study investigatesthe prevalence and distribution pattern in different acute myeloid leukemia sub- andcytogenetic groups, the association with clinical parameters and the prognosticimportance of these mutations in acute myeloid leukemia patients from south india. methods:mutation analysis was performed in 276 de novo acute myeloid leukemiapatients by polymerase chain reaction restriction fragment length polymorphism usingspecific restriction enzymes followed by sequencing to confirm the mutations. kaplan-meier survival analysis was performed to detect the prognosis. results: fms-like tyrosine kinase 3 internal tandem duplication mutations wereobserved in 20%, tyrosine kinase domain mutation in 4% and dual mutations in 0.3%of the analyzed cases. the internal tandem duplication mutations ranged from 15-107nucleotides with the majority at the juxta membrane domain of the receptor. three typesof tyrosine kinase domain point mutations were identified: d835y, d835h and d835v.we observed a significant association between fms-like tyrosine kinase 3 mutations andincreased wbc and ldh counts (p < 0.001) and blast percentage but not with age, genderand fab subtypes. a significant association with normal karyotype was observed forthe mutants (p=0.002). survival analysis revealed that the fms-like tyrosine kinase 3gene mutation was a negative prognostic marker for acute myeloid leukemia patients.the risk stratified analysis showed the mutation to be a risk factor for the intermediatekaryotype group, especially for those with normal cytogenetics. conclusion: our results indicate that the presence of an fms-like tyrosine kinase3 mutation can serve as a valuable prognostic marker in this subgroup of patients,allowing stratification for risk-directed therapy.