A 48-year-old man with chronic myeloid leukemia is started on imatinib. The drug produces durable hematologic and molecular remissions by which mechanism?

• A Inhibition of topoisomerase II causing DNA strand breaks in dividing blasts
• B Induction of apoptosis through activation of the intrinsic mitochondrial pathway independent of BCR-ABL
• C Covalent modification of the P210 fusion protein preventing dimerization
• D Competitive inhibition of the ATP-binding site of the BCR-ABL tyrosine kinase ✓

Explanation

BCR-ABL has constitutively activated tyrosine kinase activity that drives CML by activating RAS, JAK-STAT, and PI3K pathways. Imatinib mimics ATP and binds competitively to the ATP-binding pocket of the ABL kinase domain, locking it in an inactive conformation. It does not damage DNA, degrade the fusion protein, or act independently of BCR-ABL, which explains why kinase domain mutations such as T315I confer resistance.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.