A newly diagnosed patient with chronic myeloid leukemia in chronic phase is started on imatinib. The therapeutic effect of this drug results from inhibition of which molecular target?

• A JAK2-mediated signaling downstream of the erythropoietin receptor
• B Topoisomerase II-mediated DNA strand breakage
• C Dihydrofolate reductase, blocking thymidylate synthesis
• D Constitutive tyrosine kinase activity of the BCR-ABL1 fusion protein ✓

Explanation

Imatinib is a selective competitive inhibitor of the ATP-binding site of the BCR-ABL1 tyrosine kinase, the product of the Philadelphia chromosome translocation t(9;22). By blocking kinase activity it halts the proliferative signaling driving CML and produces durable hematologic and cytogenetic remissions. Topoisomerase II inhibitors are anthracyclines, methotrexate targets DHFR, and JAK2 inhibitors such as ruxolitinib are used in myelofibrosis and polycythemia vera, not CML.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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