Anaplastic large cell lymphoma (ALCL) ALK-positive shows the t(2;5)(p23;q35) translocation creating NPM1-ALK fusion. The ALK fusion protein drives lymphomagenesis primarily through constitutive activation of which signalling pathway?
- A Wnt-beta-catenin pathway
- B JAK-STAT3 pathway ✓
- C Notch1-HES1 pathway
- D Hedgehog-GLI pathway
Explanation
The NPM1-ALK fusion protein localises to both nucleus and cytoplasm (unlike membrane-bound native ALK) and constitutively activates multiple downstream pathways, with JAK-STAT3 signalling being the dominant oncogenic driver. STAT3 phosphorylation promotes anti-apoptotic gene expression (BCL-XL, survivin), cell cycle progression, and cytokine-independent proliferation. ALK+ ALCL also activates PI3K-AKT and RAS-ERK but STAT3 is the critical effector explaining sensitivity to STAT3 inhibitors. ALK inhibitors (crizotinib, brigatinib) target this fusion and are effective in relapsed ALK+ ALCL. Wnt, Notch, and Hedgehog pathways are not primary drivers in this lymphoma.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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