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.

Relationship between Bax and Bcl-2 Protein Expression and Outcome of Induction Phase Chemotherapy in Pediatric Acute Lymphoblastic Leukemia

“…Antiapoptotic proteins were more dominant than proapoptotic in 77% of pediatric ALL before diagnosis (Singh et al, 2018). Mutation of the Bcl-2 gene increases lymphocytes in the blood (Butt et al, 2017). In ALL patients who responded to chemotherapy, Bcl-2 protein expression was lower than the unresponsive group, namely 60.2% vs. 92.2% (Aref et al, 2004).…”

“…The development in pediatric ALL management over the last decade has succeeded in improving chemotherapy outcomes, although the mortality rate is still relatively high. The highest incidence and mortality of leukemia was in Asia (Namayandeh et al, 2020) and the predominant in boys (Butt et al, 2017;Singh et al, 2018;Jaime-Pérez et al, 2018;Kakaje et al, 2020;Namayandeh et al, 2020).…”

Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study

“…The Bax G (−248) A rs4645878 SNP ARMS primers were designed by using Primer 3 software. For Bcl-2 rs2279115C>T, ARMS primers were previously used by Butt et al [42], for TNF-α rs1800629 G>A as well as for IL-8 rs4073 T>A SNPs, ARMS primers were previously used by Matheson et. al.…”