Introduction: Introduction :Chronic Lymphocytic Leukemia (CLL) is a type of cancer that starts in the bone marrow and affects the blood and lymphatic system. It is characterized by the overproduction of abnormal white blood cells, which can crowd out healthy cells and impair the immune system's ability to fight infection. CLL is typically a slow-growing cancer, with symptoms often not appearing until later stages of the disease
Methods: Methods: A comprehensive bioinformatics–based investigation was conducted to identify genetic determinants associated with chronic lymphocytic leukemia (CLL). Disease-related genes were systematically retrieved from the NCBI database. Single nucleotide polymorphisms (SNPs) and corresponding rsIDs were curated and analyzed using the MegaGene platform to explore allelic variation patterns, predicted functional impacts, and pathway involvement.
Simultaneously, an exhaustive literature and pharmacological data review was conducted for Lifoza, currently the sole CLL therapy available in Iran. Reported adverse drug reactions (ADRs) were extracted and evaluated for pharmacogenomic associations via the Pharmacogenomic Observed Genetic Hits (POHG) framework.
Results: Results: Bioinformatic analysis revealed statistically significant associations between CLL pathogenesis and polymorphisms in TP53, STAT3, and ABCB1. Notably, ABCB1 polymorphisms have been implicated in modulating drug response and toxicity in other hematological malignancies—such as multiple myeloma treated with lenalidomide—highlighting their potential pharmacogenomic relevance.
Clinical data review for Lifoza showed a high prevalence of serious adverse effects (renal failure, cardiac disease, kidney fibrosis, hepatic dysfunction). However, POHG analysis found no direct pharmacogenomic correlations between these toxicities and the evaluated genetic variants.
Conclusion: Conclusion: Although no definitive pharmacogenomic markers were found to predict Lifoza-related toxicities, the severity and frequency of observed ADRs emphasize the clinical importance of pre-treatment pharmacogenomic stratification. Incorporating genetic screening—especially given the relevance of drug transporter genes like ABCB1 in treatment outcomes—could enhance patient safety, optimize therapeutic choices, and reduce adverse events.