New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance
Imatinib resistance in chronic myeloid leukemia is driven by BCR‑ABL-dependent and -independent mechanisms, and newer tyrosine‑kinase inhibitors such as dasatinib and nilotinib may overcome these resistance pathways.
Chronic myeloid leukemia (CML) was the first human malignant disease linked to a single, acquired genetic abnormality, the BCR‑ABL kinase fusion protein. Targeted therapy with imatinib, a selective BCR‑ABL inhibitor, has been a major success but patients with advanced disease often exhibit resistance and relapse. Resistance arises from BCR‑ABL-dependent mechanisms (gene amplification, overexpression, mutant isoforms) and BCR‑ABL-independent pathways (e.g., other kinases such as Src family members). Newer tyrosine‑kinase inhibitors, dasatinib (multitargeted BCR‑ABL and Src inhibitors) and nilotinib (selective BCR‑ABL), show promise in overcoming these resistance mechanisms.
Understanding the mechanisms of imatinib resistance is essential for improving therapeutic strategies in CML, especially for patients with advanced disease who are at risk of poor outcomes.
Bizonyítékszint: Állatkísérletes. Állatmodellben vizsgálták.
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