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Imatinib (IM) was approved as a molecular target drug that selectively inhibits Bcr-Abl tyrosine kinase which causes Philadelphia-positive chronic myeloid leukemia (CML) and so far been the first-choice treatment in CML with excellent results. However, only a proportion of patients achieve major molecular response. Hence, the need to find whether there are some factors that affect the response to treatment is essential. Although IM pharmacokinetics is influenced by several enzymes and transporters, little is known about the role of pharmacogenetic variation in IM metabolism.

We investigated the mutational status of SLCO1 and CYP3A5 by Polymerase Chain Reaction followed by restricted fragment length polymorphism in 62 Philadelphia positive newly diagnosed Egyptian CML patients in chronic phase. All patients received imatinib therapy and were followed for at least one and half years. The response to imatinib therapy was evaluated by recording the hematological response, cytogenetic response at 6 month, and molecular response at 12 month of imatinib treatment according to the European Leukemia Net criteria.

11 patients were excluded from the study as they showed treatment failure to imatinib at 6 month of treatment so they were shifted to 2nd line TKIs. Six (54.5%) out of these 11 patients were mutant for CYP3A5 while five were wild, however four (36.3%) out of them were mutant for SLCO1 and seven patients were wild type. The remaining 51 patients who continued in the study showed that the mutant CYP3A5 was more common with low hemoglobin level (P 0.03) and low platelets count at diagnosis (P 0.001) however, there was no relation between SLCO1 mutational state and patients characteristics. Also there was no relation between mutational state of either CYP3A5 or SLCO1 with the sokal score of the patients at diagnosis. Patients with mutant CYP3A5 showed suboptimal cytogenetic response to imatinib at 6 month versus patients with wild type (P 0.07). At 12 month of imatinib treatment, 74.1% of patients with mutant CYP3A5 had no MMR versus 66.7% of patients with wild type had MMR (P 0.004). However there was no significant relation between mutational state of SLCO1 with neither cytogenetic response at 6 month nor molecular response at 12 month of imatinib treatment.       

CYP3A5 mutant gene was associated with poor imatinib efficacy while the SLCO1 was not associated with the response to imatinib treatment in Egyptian patients with CML in chronic phase.