Reed-Sternberg (RS) cells in classic Hodgkin lymphoma are derived from germinal center B cells but have lost B-cell identity. Which transcription factor, normally critical for B-cell identity, is silenced in RS cells through epigenetic mechanisms, contributing to their aberrant phenotype?
- A IRF4 (MUM1)
- B PAX5 ✓
- C NF-κB
- D BLIMP1
Correct answer: B. PAX5
Explanation
PAX5 (BSAP) is the master transcription factor for B-cell identity that maintains B-cell gene expression programs including CD20, CD79a, and immunoglobulin receptor signalling components. In classic Hodgkin lymphoma, PAX5 is epigenetically downregulated (promoter hypermethylation and loss of activating marks) in Reed-Sternberg cells, which explains why RS cells lose normal B-cell markers like CD20 and CD79a while gaining aberrant expression of T-cell markers such as CD15 and CD30. NF-κB is constitutively activated in RS cells, contributing to survival.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.