Mutations of FLT 3 Gene in Pakistani Acute Myeloid Leukemia Patients

Abstract

ABSTRACT:

Background: Acute myeloid leukemia, AML, is a hematological malignancy, with diverse genetic abnormalities. Mutations in FLT3 gene are the most common aberrations found in AML. The two important FLT3 mutations are ITD and D835 mutation. Both of these mutations are of prognostic significance in AML and are target of currently developing new drugs which are part of strategies to improve outcome of AML patients.

Objectives: The objective of this study was to determine the frequency of ITD and D835 mutations of FLT3 gene in AML patients in Pakistani population.

Methodology: 47 untreated and diagnosed male and female AML patients of all age groups were included in the study. After DNA extraction, exons 14 and 15 (for ITD) and exon 20 (for D835) of FLT3 gene were amplified by PCR. For ITD mutation detection, PCR products were analyzed by amplified fragment length polymorphism analysis, while D835 mutations were detected by restriction fragment length polymorphism by using EcoRV restriction enzyme.

Results: Frequencies of both FLT3/ITD and FLT3/D835 mutations were found to be 6.4%. ITD mutation shows a significant association with old age and high WBC count.

Conclusion: The frequency of FLT3/ITD mutations, found in the present study, is lower than that reported in other studies, while that of D835 mutation is within the range observed by most researchers. This lower ITD frequency than usual while normal D835 frequency showed the possibility that, instead of ITD mutation, other mutations of the FLT3 gene (like D835) may be more common in the local population.