Imatinib achieves durable responses in chronic myeloid leukemia through which primary mechanism of action?

• A Irreversible alkylation of DNA in proliferating myeloid precursors
• B Blockade of the IL-3 receptor on progenitor cells
• C Inhibition of topoisomerase II leading to double-strand breaks
• D Competitive inhibition of the ATP-binding site of the BCR-ABL1 tyrosine kinase ✓

Explanation

Imatinib is a targeted small molecule that occupies the ATP-binding pocket of the BCR-ABL1 fusion protein, preventing phosphorylation of downstream substrates and halting the proliferative signal that drives CML. It also inhibits PDGFR and c-KIT, explaining activity in gastrointestinal stromal tumors. Alkylators and topoisomerase II inhibitors are conventional cytotoxics without specificity for BCR-ABL1, and IL-3 receptor blockade plays no role in current CML therapy.

Reference: Katzung Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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