Which of the following best describes the mechanism of action of imatinib in chronic myeloid leukemia?

• A It irreversibly alkylates DNA at the O6 position of guanine
• B It inhibits topoisomerase II and causes double-strand DNA breaks in dividing blasts
• C It binds CD20 on malignant B cells and mediates complement-dependent lysis
• D It competitively occupies the ATP-binding pocket of the BCR-ABL1 tyrosine kinase domain ✓

Explanation

BCR-ABL1 is a constitutively active tyrosine kinase. Imatinib mimics the adenine portion of ATP and fits into the ATP-binding cleft of the kinase domain, locking it in an inactive conformation and preventing phosphorylation of downstream substrates. Topoisomerase II inhibition describes etoposide, anti-CD20 activity describes rituximab, and guanine alkylation describes agents such as temozolomide, none of which act on this target.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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