Which translocation in CML results in a constitutively active tyrosine kinase and is the direct molecular target of imatinib?
- A t(9;22) producing BCR-ABL1 (p210) fusion protein ✓
- B t(15;17) producing PML-RARA fusion protein
- C t(8;14) producing MYC overexpression
- D t(14;18) producing BCL2 overexpression
Correct answer: A. t(9;22) producing BCR-ABL1 (p210) fusion protein
Explanation
CML is caused by t(9;22)(q34;q11.2) — the Philadelphia chromosome — creating the BCR-ABL1 fusion gene, most commonly producing p210 (occasionally p190 in ALL, p230 in CNL). The BCR-ABL1 fusion protein is a constitutively active non-receptor tyrosine kinase that drives uncontrolled myeloid proliferation. Imatinib (and subsequent TKIs) competitively inhibit the ATP-binding pocket of ABL1. t(15;17) is APL; t(8;14) is Burkitt lymphoma; t(14;18) is follicular lymphoma.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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