Hairy cell leukemia (HCL) has a near-universal somatic mutation in BRAF V600E. Which statement about the role of this mutation in HCL biology and therapy is MOST accurate?

• A BRAF V600E mutation in HCL activates PI3K-delta signalling, making idelalisib the preferred targeted therapy
• B BRAF V600E causes constitutive NFκB activation, and bortezomib achieves complete remissions in all HCL patients
• C BRAF V600E activates the MAPK/ERK pathway constitutively and is the target of vemurafenib, which is effective as salvage therapy in relapsed/refractory HCL ✓
• D BRAF V600E is a passenger mutation in HCL; cladribine efficacy is independent of BRAF status

Explanation

BRAF V600E is present in virtually all classic HCL cases and constitutively activates the MAPK/ERK signalling cascade, driving leukemic cell proliferation and survival. Vemurafenib (a BRAF V600E inhibitor) produces clinical responses in relapsed/refractory HCL, validating BRAF as the key oncogenic driver. The mutation activates MAPK, not PI3K-delta or NF-κB directly. While cladribine remains standard first-line treatment, BRAF inhibition is an important salvage option, and BRAF V600E is the defining driver (not a passenger mutation) that also helps distinguish classic HCL from HCL variant.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.