Polymorphisms of BCL2 Gene in Acute Lymphoblastic Leukemia Patients in Pakistan and Screening of Phytochemicals to Overcome its Expression

Abstract

Leukemia is a third fatal disease in developing countries. According to Punjab cancer registry 2014 report, leukemia incidence in Pakistan is 18.8%. Many treatments are available for leukemia now days but still there is a mortality rate measured. BCL2 controls cell apoptosis but when overexpressed due to the presence of promoter region single nucleotide polymorphism 938C>A, it causes anticancer drug resistance and represses apoptosis of malfunctioned cells resulting in immature leucocytes. The aim of the present study was genotyping of promoter region SNP in acute lymphoblastic leukemia patients of Pakistan and screening of naturally occurring phytochemical to identify BCL2 active site targeting compounds to control its expression. Study was performed on 104 cases taking similar control size showing allelic frequency C=0.466 and A=0.534 in cases, indicating an association with the disease by having chi-square p-value 0.0032. Screening of 90 phytochemicals was performed out of which one compound was selected as a lead compound based upon drug likeliness properties, binding with protein, and natural existence that may cause the least harm to human body and greater effect on leukemia cells. The information provided by this research can be used to make new-targeted drugs to control leukemia by inhibiting the mutated proteins.