A 68-year-old man presents with splenomegaly, leucocytosis of 85,000/μL with full myeloid spectrum, basophilia, and a Philadelphia chromosome (t(9;22)) on cytogenetics. He is started on imatinib. What is the mechanism of action of imatinib?
- A Inhibition of JAK2 kinase
- B Competitive inhibition of BCR-ABL tyrosine kinase ATP binding site ✓
- C Alkylation of DNA causing double-strand breaks
- D Inhibition of BCL-2 anti-apoptotic protein
Correct answer: B. Competitive inhibition of BCR-ABL tyrosine kinase ATP binding site
Explanation
Imatinib is a selective BCR-ABL tyrosine kinase inhibitor that competitively binds the ATP-binding pocket of the BCR-ABL fusion protein, blocking its constitutively active kinase activity and downstream pro-proliferative signaling in CML. It also inhibits c-KIT and PDGFR. JAK2 inhibitors (ruxolitinib) are used in myelofibrosis; alkylating agents are cytotoxic chemotherapy; venetoclax inhibits BCL-2 (used in CLL and AML).
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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