In polycythaemia vera (PV), which mutation is found in nearly 95% of patients, and what signalling pathway does it constitutively activate?
- A JAK2 V617F point mutation; constitutively activates JAK-STAT pathway ✓
- B BCR-ABL1 fusion; activates ABL tyrosine kinase
- C CALR exon 9 mutation; activates MPL/thrombopoietin receptor
- D FLT3-ITD mutation; activates PI3K-AKT pathway
Correct answer: A. JAK2 V617F point mutation; constitutively activates JAK-STAT pathway
Explanation
The JAK2 V617F point mutation (valine to phenylalanine substitution at codon 617 in exon 14) is present in ~95% of PV and ~50–60% of essential thrombocythaemia and primary myelofibrosis. This gain-of-function mutation causes constitutive activation of the JAK2-STAT5 signalling pathway, leading to cytokine-independent erythropoiesis. CALR mutations are found in JAK2-negative ET and PMF. BCR-ABL1 characterises CML. FLT3-ITD is associated with AML. The JAK2 V617F allele burden correlates with disease severity in PV.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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