Abstract in English:

Abstract Introduction Treatment resistance has become increasingly common in patients with chronic myeloid leukemia. Lack of response to tyrosine kinase inhibitors is associated with mutations in the BCR::ABL1 kinase domain. This study aims to report the frequency and types of BCR::ABL1 kinase domain mutations in Pakistani chronic myeloid leukemia patients. Materials and methods This prospective study was conducted from January to June 2025 at the Armed Forces Institute of Pathology in Pakistan. It included adult patients with chronic myeloid leukemia who were non-responsive to treatment based on molecular, hematological, and clinical criteria. Allele-specific real-time polymerase chain reaction was performed to detect four kinase domain mutations: T315I, E255V, E255K and Y253H. Data was analyzed using IBM SPSS v23. Results The mean age of the 133 treatment-resistant chronic myeloid leukemia patients included in the study was 47.3 ± 13.6 years. The majority of cases (62.4%) were male and 79 (59.4%) patients were currently on imatinib therapy. The median BCR::ABL1 level, as measured by quantitative polymerase chain reaction, was 30.73% (range: 1.17-100%) International Scale. BCR::ABL1 kinase domain mutations were detected in 57 (42.9%) patients. E255K was the most common mutation detected in 45 (33.8%) cases, followed by E255V in 11 (8.3%), T315I in 1 (0.8%) and the Y253H mutation in 1 (0.8%) patient. The presence of kinase domain mutations was significantly associated with higher total leucocyte count (p = 0.002), while the E255K mutation was significantly associated with blast crisis (p = 0.048). Conclusion This study revealed a high prevalence of BCR::ABL1 kinase domain mutations in Pakistani chronic myeloid leukemia patients. E255K, the most frequently detected mutation, was significantly associated with blast crisis. These findings underscore the significance of molecular testing for personalized treatment.