A 65-year-old man has fatigue, splenomegaly, WBC 130,000/µL with the full myeloid series, basophilia, and BCR-ABL1 fusion without JAK2 mutation. The pathophysiological consequence of BCR-ABL tyrosine kinase is:
- A Inactivation of STAT5 causing a block in differentiation at the myeloblast stage
- B Upregulation of BCL2 exclusively via JAK2-STAT3 signaling
- C Constitutive activation of PI3K/AKT and RAS/MAPK pathways, suppressing apoptosis and driving uncontrolled myeloid proliferation ✓
- D Loss of CEBPA causing neutrophil maturation arrest
Correct answer: C. Constitutive activation of PI3K/AKT and RAS/MAPK pathways, suppressing apoptosis and driving uncontrolled myeloid proliferation
Explanation
BCR-ABL1 is a constitutively active tyrosine kinase that activates PI3K/AKT (anti-apoptotic), RAS/MAPK (proliferation), and STAT5 (survival) pathways in a growth-factor-independent manner, driving unrestrained myeloid proliferation with preserved differentiation. CML blast crisis involves additional mutations blocking differentiation. JAK2 mutations define myeloproliferative neoplasms like PV and ET; CEBPA mutations cause differentiation block in AML.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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