Study of Fragile Histidine Triad (FHIT) gene Promoter DNA Methylation in Acute Lymphoblastic Leukemia (ALL) patients

FHIT gene Promoter DNA Methylation in ALL

Abstract

Background: The fragile histidine triad (FHIT) gene has earlier been projected as a tumor suppressor in many disease mechanisms including acute lymphoblastic leukemia (ALL). DNA methylation at in the promoter region of FHIT gene has been linked with gene silencing, and hence its inactivation is responsible in the pathogenesis of many kinds of human malignancies. We first time from the Indian subcontinent evaluated the frequency of FHIT hypermethylation in a cohort of ALL cases from Kashmir region (North India).

Methods: FHIT gene hypermethylation was investigated in a cohort of 66 confirmed ALL patients at diagnosis by methylation specific PCR (MSP-PCR).

Results: Our results significantly showed FHIT promoter methylation was considerably higher in ALL subjects with a frequency of 80% (53 of 66). FHIT gene promoter methylation was seen higher in males 84% as compared to females 75%. Older age group (≥25years) patients showed higher 87% FHIT gene hypermethylation as compared to 78% in lower age group (<25 years. Around 94% of subjects harboring hypermethylated FHIT gene were having higher WBC count as compared  to cases with lower WBC count  (p>0.05).

Conclusion: We conclude that FHIT gene hypermethylation is highly implicated in ALL cases and seems as an initial event in the ALL pathogenesis