Role of genetic factors in imatinib resistance of chronic myeloid leukemia: P53, RB1, ASS1 gene deletions, and chromosome 8 hyperdiploidy

Abstract

Additional genetic mutations alongside the BCR/ABL1 fusion gene in chronic myeloid leukemia (CML) patients suggest clonal evolution associated with disease progression. This study investigates the molecular determinants of imatinib resistance and disease progression in CML patients. Upon analyzing 141 study subjects undergoing imatinib therapy, encompassing both resistant cases and those showing favorable responses, a notable association emerged between certain genetic markers—such as P53 deletion and hyperdiploidy of chromosome 8—and resistance to imatinib therapy. Notably, patients with these genetic abnormalities experienced poor outcomes, particularly during blast crises. Conversely, RB1 gene mutations were absent in all cases and no direct association between ASS1 gene deletion and imatinib treatment resistance was observed. These findings emphasize the clinical relevance of identifying additional abnormalities alongside BCR/ABL1 translocation for predicting disease progression and guiding treatment strategies in CML.