BET bromodomain inhibition in MPN
Current understanding
BET (bromodomain and extra-terminal) proteins (BRD2/3/4) act as epigenetic readers of acetylated histones that scaffold transcription of inflammatory, fibrotic, and proliferative gene programs (NF-κB targets, MYC, TGF-β-responsive genes) implicated in MPN pathobiology. Pharmacologic BET inhibition, led clinically by pelabresib (CPI-0610), has shown phase 2–3 activity in myelofibrosis when added to ruxolitinib, supporting a model in which BET-dependent transcriptional output is a complementary, JAK-STAT-orthogonal arm of MPN clonal and stromal disease. Hematologic toxicity and durable survival/disease-modification benefit remain unresolved.
Evidence log
- 2026-07-01 — DDX5: a versatile RNA helicase in cancer and cell fate determination-linking c-Myc and JAK2 V617F signalling to emerging therapeutics.: cross-connection with jak-stat-signaling: DDX5 acts as a scaffolding co-activator linking JAK2 V617F signaling to c-Myc transcriptional output, mechanistically converging with BET inhibitor rationale that targets MYC-driven proliferative programs left intact by JAK inhibition. (novelty: 4)
- 2026-06-05 — The impact of novel bet inhibitors on the treatment armamentarium of Myelofibrosis.: cross-connection with jak-stat-signaling: Pelabresib + ruxolitinib combinations operationalize the model that BET-dependent transcription is a parallel, JAK-STAT-orthogonal driver of MF clonal output. (novelty: 3)