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MOLECULAR AND LABORATORY FEATURES OF CHRONIC MYELOID LEUKEMIA PATIENTS WITH TKI RESISTANCE MUTATIONS AT THE NATIONAL INSTITUTE OF HEMATOLOGY AND BLOOD TRANSFUSION (2020–2024)
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Abstract
Introduction: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the BCR::ABL1 fusion gene, resulting from the Philadelphia chromosome translocation. Targeted therapy with tyrosine kinase inhibitors (TKIs) has significantly improved clinical outcomes; however, drug resistance—particularly due to BCR::ABL1 mutations—remains a major therapeutic challenge. Objective: To describe the genetic alterations in CML patients harboring resistance-associated mutations at the National Institute of Hematology and Blood Transfusion during the period 2020–2024. Methods: A retrospective cross-sectional study was conducted on 38 CML patients with confirmed TKI resistance mutations, identified through next-generation sequencing (NGS). Results: Among the 38 patients, 57.5% had a single mutation, 27.5% had two mutations, and 15% carried three resistance mutations. The most frequent mutations included Y253H, G250E, F359V, and T315I, predominantly located in the P-loop, C-loop, and the Imatinib-binding domain of the BCR::ABL1 protein. In addition to point mutations, cases of insertion/deletion mutations were also identified. Conclusion: Next-generation sequencing is a crucial tool for detecting TKI resistance mutations in CML patients. The detected mutations were highly heterogeneous and significantly influenced treatment outcomes. Personalized therapy guided by mutation profiling is essential to optimize efficacy and improve prognosis in patients with TKI-resistant CML.
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Keywords
Chronic myeloid leukemia (CML), Tyrosine kinase inhibitors (TKI), Next-Generation Sequencing (NGS), Resistant mutations
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