BCR-ABL GENE KINASE DOMAIN MUTATION FREQUENCY IN IMATINIB RESISTANT CHRONIC MYELOID LEUKEMIA PATIENTS

Background. BCR-ABL gene mutations are the main course of tyrosine kinase 1^st generation inhibitor (TKI-1) imatinib resistance in chronic myelogenous (CML) patients. Some of them are resistant both for imatinib and TKI-2. The nilotinib and dasatinib mutation spectra are not the same. To ensure a correct choice of TKI-2 for imatinib CML resistant patient treatment it is necessary to investigate frequency of BCR-ABL gene mutations. Aim. To evaluate BCR-ABL gene mutation frequency in imatinib resistant CML patients. Materials and methods. Peripheral blood of imatinib resistant CML patients were studied by means of direct PCR product Sanger sequencing in order to reveal BCR-ABL gene mutations. Results. BCR-ABL gene mutations were found in 31 % (n=262/846) imatinib resistant patients. Proportion of resistant mutations were 40,3 % for nilotinib and 21 % for dasatinib. Conclusion. More than a halve of BCR-ABL mutations resistant for imatinib were resistant either against nilotinib or dasatinib. Consequently, prior to replace imatinib for nilotinib or dasatinib it is necessary to perform BCR-ABL mutational analysis. If to prescribe TKI-2 blindly there may be high risk that nilotinib or dasatinib would be ineffective due to improper mutation in BCR-ABL gene.

хронический миелолейкоз, резистентность к иматинибу, мутация гена BCR-ABL, chronic myelogenous, imatinib resistance, BCR-ABL gene mutation

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