glance at the pharmacogenetics of chronic myeloid leukemia

Cancer is multifactorial illness. These factors include genetic, inflammation,environmental factors, life style, and aging. Cancer is in fact genetic disease that is due to changesin genes that control the function, growth, and division of cells. Chronic myeloid leukemia (CML)is stem cell disorder caused due to the continuous function of tyrosine kinase domain in BCRABL fusion oncogene, resulting from reciprocal translocation of Ch. and 22 t(9;22)(q34;q11).Increased tyrosine kinase activity causes abandoned cell proliferation via downstream pathwayssuch as RAS, RAF, JUN kinase, MYC, and STAT. The incidence of CML is 1-2 cases per 100,000adults, and about 15% of newly diagnosed leukemia cases in adults.CML consists of three phases:chronic phase (CP), accelerated phase (AP), blast phase (BP). Common symptoms occur in thechronic phase, which makes it possible to diagnose the disease in the chronic phase. Commonsymptoms include weight loss, fatigue, insomnia, obstruction, and etc. Initially, treatment of chronicmyeloid leukemia was performed by stem cell transplantation and interferon alpha. However, nowtherapies targeting the tyrosine kinase domain are used instead. Tyrosine Kinase inhibitors includeimatinib, nilotinib, dasatinib, gefitinib and etc.Using specific drug, the responses of the patients as well as the risk of the side effects mayvary between different patients. These differences are due to several factors including the diversegenetic profile of each patients. Pharmacogenetic is the treatment of the patients based on their genetic background. The individualized treatment of the cancer patients can be used to improvetheir therapeutic efficacy and reduce side effects.Imatinib (as an oral TKI) is currently used as the first generation treatment of Philadelphiapositive CML patients and also for GIST patients harboring specific mutations in the c-KIT andPDGFRA genes. However, about 2-4% of patients develop resistance. General categories of genessuch as drug metabolizing enzymes (cytochrome P450, glucuronides transferase), effluxtransporters (ABCB1/MDR1/P-glycoprotein/Pgp and ABCG2/BCRP) and the influx transporterOCT1/SLC22A1 (human organic cation transporter 1) can be effective in predicting response toimatinib treatment. In addition to genes, biomarkers and epigenetics are also effective in respondingto treatment. Biomarkers include predisposition markers, diagnostic markers, prognostic markers,and therapeutic markers. Despite many studies on the factors influencing the response to imatinibtreatment, there are still number of patients who are resistant to the drug. So more studies have tobe done on the pharmacogenetics of the genes seems to be effective in responses to this drug.