Pharmacogenomics of Leukemia; Unlocking Personalized Treatment Strategies

Abstract

Leukemia, a diverse group of blood cancers, continues to present significant challenges in diagnosis and treatment. Recent advancements in pharmacogenomics have opened new avenues for tailoring therapeutic strategies to individual patients' unique genetic and molecular characteristics. In leukemia, genetic polymorphisms have been identified that influence drug metabolism, efficacy, and the risk of adverse effects. Notable examples include TPMT variants affecting thiopurine treatment in acute lymphoblastic leukemia (ALL), UGT1A1 polymorphisms impacting irinotecan toxicity in acute myeloid leukemia (AML), and SLCO1B1 variants influencing methotrexate response in ALL. Targeted therapies have revolutionized leukemia treatment, focusing on specific genetic abnormalities. Tyrosine kinase inhibitors (TKIs) like imatinib have successfully treated chronic myeloid leukemia (CML) with the BCR-ABL fusion gene. Similarly, immunotherapies, such as CAR T-cell therapy, reshape treatment paradigms for B-cell ALL. The personalized approach minimizes adverse effects while optimizing treatment efficacy. Moreover, genetic markers are aiding in identifying patients at higher risk of developing cardiotoxicity from anthracycline chemotherapy. This article provides an overview of the evolving landscape of pharmacogenomics in leukemia, highlighting key findings and trends. Combinatorial therapies, biomarker discovery, and patient-centric care are expected to enhance outcomes and survivorship.