Imatinib (Gleevec) revolutionised CML treatment by targeting which specific molecular abnormality?

• A Inhibits JAK2 kinase in the JAK-STAT pathway mutated in BCR-ABL negative MPNs
• B Blocks CD20 on malignant B-lymphocytes triggering antibody-dependent cytotoxicity
• C Inhibits proteasome 26S resulting in accumulation of pro-apoptotic proteins in plasma cells
• D Inhibits the constitutively active BCR-ABL tyrosine kinase product of the Philadelphia chromosome t(9;22) translocation ✓

Explanation

The Philadelphia chromosome [t(9;22)(q34;q11)] fuses the BCR gene with the ABL1 proto-oncogene, producing the constitutively active BCR-ABL tyrosine kinase that drives CML pathogenesis. Imatinib is a first-generation ABL tyrosine kinase inhibitor (TKI) that competitively occupies the ATP-binding site of BCR-ABL in its inactive conformation, blocking downstream proliferation signals. This molecularly targeted therapy marked a paradigm shift in oncology. JAK2 inhibitors (e.g., ruxolitinib) treat BCR-ABL negative MPNs (PV, MF). Rituximab targets CD20; bortezomib inhibits the proteasome.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.