Frequency of FLT3/ITD Mutations in Pakistani Acute Myeloid Leukemia Patients

Acute myeloid leukemia (AML) is characterized by an increase in the number of myeloid cells in the marrow and an arrest in their maturation. FLT3 gene, a member of the class III receptor tyrosine kinase family, plays an important role in stem cell survival, and the development of dendritic and natural killer cells. Internal tandem duplication (ITD) mutations result from the duplication and tandem insertion of a portion of the juxtamembrane region (exons 14 to 15) of the FLT3 wild-type gene and occur in 20 to 30% of patients. These mutations are associated with worse prognosis. The aim of this project was to study the spectrum of these mutations in Pakistani AML patients and correlate them with clinical findings. Blood samples of 100 AML patients from different hospitals of Lahore were included in this study. For screening of mutations, a 329 base pair fragment covering FLT3 exons 14 and 15 of known wild type and mutant-positive samples were PCR amplified. FLT3/ITD mutations were found in 17% AML patients. These mutations did not correlate significantly with age or sex, though the incidence was higher in female patients. These mutations were significantly associated with high WBC count and high blast percentage. The overall incidence of FLT3/ITD mutations was lower in Pakistani patients but was within the globally reported ranges. Like the developed countries of the world, AML patients in Pakistan should also be screened for the presence of these mutations so that proper treatment strategies could be adopted.