A 52-year-old man with chronic myeloid leukaemia is started on imatinib and achieves a complete cytogenetic remission. The molecular target of imatinib is:
- A The SH2 domain of the ABL portion of the fusion protein
- B The ATP-binding site of the constitutively active BCR-ABL tyrosine kinase ✓
- C Ras prenylation at the carboxy terminus of K-RAS
- D Topoisomerase II, preventing replication of the Philadelphia chromosome
Correct answer: B. The ATP-binding site of the constitutively active BCR-ABL tyrosine kinase
Explanation
BCR-ABL is a constitutively active tyrosine kinase produced by the t(9;22) translocation. Imatinib competitively occupies the ATP-binding pocket of this kinase, blocking phosphorylation of downstream substrates and halting proliferation of leukaemic cells. The other options describe targets or domains that imatinib does not bind: Ras prenylation is targeted by farnesyl transferase inhibitors experimentally, and topoisomerase poisons are unrelated to this drug.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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