MUTATIONAL STATUS AND TREATMENT EFFICACY IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA.

[BACKGROUND] The use of targeted therapy for chronic myeloid leukemia (CML) - tyrosine kinase inhibitors (TKIs) - has led to significant success in the treatment of patients with CML. The life expectancy of patients with newly diagnosed CML is almost equal to that of the general population. A significant proportion of patients on TKI therapy achieve stable and long'term remission, and after two or more years, it is possible to safely discontinue therapy. The increase in patient life expectancy has contributed to an increased risk of developing resistance to therapy, which is largely associated with mutations in the kinase domain of the BCR::ABL1gene, which are of decisive clinical importance.The objectiveof this article is to evaluate the role of the mutation status of the kinase domain of the BCR::ABL1gene and other somatic mutations in patients with CML in the development of resistance to tyrosine kinase inhibitors and the impact of mutations on treatment efficacy based on literature data.

[DATA SOURCES] The study used publications from 2015-2025, selected from the PubMed and Scopus databases and specialized scientific journals using the keywords (chronic myeloid leukemia, BCR::ABL1, tyrosine kinase inhibitors (TKIs), T315Imutation, TKI resistance, mutation status, imatinib, dasatinib, nilotinib, ponatinib, asciminib).

[STUDY SELECTION] After reviewing the full texts of the articles, those that directly addressed the mutation status in CML, as well as some general aspects of CML (pathogenesis, clinical course, diagnosis, treatment), were selected for further analysis.

[RESULTS] The analysis demonstrated a high prevalence of clinically significant mutations, particularly T315I, which cause resistance to TKIs. The available data indicate that third' and fourth'generation TKIs, in particular ponatinib, as well as the new allosteric inhibitor asciminib, have significant potential in the treatment of patients with resistant forms of CML, including carriers of the T315Imutation. There are cases of compound mutations that remain a serious therapeutic challenge. To effectively combat resistant clones, it is necessary to determine the mutation status and select therapy according to the sensitivity of the clone.

[CONCLUSIONS] A personalized approach that takes into account the BCR::ABL1mutation profile is key to optimizing therapeutic strategies for CML. Further research is needed to more clearly define the mechanisms of resistance and the optimal sequence of use of available TKIs in clinical practice.