Investigation of the Possible Role of Genetic Polymorphism in Certain Metabolizing Enzymes and Membrane Transporters on Both Plasma Level and Molecular Response of Imatinib in Patients With Chronic Myeloid Leukemia

Introduction:

Chronic myeloid leukaemia (CML) is a myeloproliferative disease with an incidence of one to two cases per 100,000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.

The introduction of imatinib, the tyrosine kinase inhibitor (TKI), in the early 21st century is considered a breakthrough in the treatment of CML. In the vast majority of patients, treatment with imatinib induces cytogenetic and even molecular responses with very low or undetectable BCR-ABL1 transcript levels. These patients remain free from progression to blast crisis. However, imatinib does not cure the disease because it is unable to eradicate the leukaemic stem cells, which therefore provides a potential reservoir for relapse.

Despite its efficacy and favorable pharmacokinetic profile, there is a large inter-individual variability in imatinib plasma concentrations, which may lead to treatment failure and disease progression.

Polymorphisms in genes related to absorption, distribution, metabolism and excretion of imatinib may affect the bioavailability and consequently the response to the drug.