Cytogenetic profile of chronic myeloid leukaemia patients resistant to imatinib at tertiary level in Indonesia.

Abstract

Background: Chronic Myeloid Leukemia (CML) is primarily driven by the Philadelphia chromosome, producing the BCR::ABL1 fusion protein. Although imatinib significantly improved CML outcomes, resistance remains a key challenge. Resistance often leads to cytogenetic abnormalities (ACAs), indicating poor disease prognosis. This is the first study that investigates genetic profiles in imatinib-resistant Indonesian CML patients.

Method: The study included adult chronic-phase CML patients who met the criteria of treatment failure under the treatment of imatinib. Peripheral blood samples and bone marrow samples were collected and then processed for cytogenetic examination following the International System of Human Cytogenetic Nomenclature (ISCN) guidelines. BCR::ABL1 transcript levels were measured using Quantitative Real-Time PCR.

Result: Out of 27 CML patients, the mean age was 39.15 years, with a male-to-female ratio of 1:1.5. The mean BCR::ABL1 international scale (IS) value was 37.20 ± 4.56, and patients on tyrosine kinase inhibitor (TKI) therapy had a median treatment duration of 80 months. Cytogenetic analysis showed Philadelphia chromosome (Ph) positivity in 11.11% of peripheral blood and 34.78% of bone marrow samples, with Ph negativity in 25.93% and 17.93%, respectively. Peripheral blood abnormalities included trisomy 8 (11.11%), additional Ph (7.41%), trisomy 19 (3.70%), and complex karyotypes (14.81%), while bone marrow abnormalities included trisomy 8 (13.04%), additional Ph (8.69%), trisomy 21 (4.35%), monosomy 7/7q- (8.70%), and complex karyotypes (43.45%).

Conclusion: Cytogenetic anomalies such as trisomy 8, trisomy 19, and complex karyotypes may contribute to TKI resistance. Further study is needed to understand additional abnormalities observed.