Hairy cell leukemia (HCL) characteristically shows which specific molecular mutation in virtually 100% of cases, now included in its WHO diagnostic criteria?

• A BRAF V600E point mutation ✓
• B JAK2 V617F point mutation
• C MYD88 L265P mutation
• D NOTCH1 mutation

Explanation

BRAF V600E substitution (valine to glutamate at codon 600) is present in virtually 100% of classic HCL cases and is now a WHO-recognized diagnostic criterion. This mutation constitutively activates the RAF-MEK-ERK (MAPK) pathway, driving proliferation. Clinically, this has therapeutic implications: BRAF inhibitors (vemurafenib) are effective in relapsed/refractory HCL. JAK2 V617F is the hallmark of myeloproliferative neoplasms (PV, ET, MF); MYD88 L265P is characteristic of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia; NOTCH1 mutations are found in T-ALL and some CLL cases.

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

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Written and medically reviewed by the StethoPrep medical team.