TGF-β superfamily signaling in MPN
Current understanding
To be populated as evidence accumulates.
Evidence log
- 2026-09-01 — Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia.: In JAK2V617F MF models, pitavastatin-mediated fibrocyte depletion coincides with reduced TGF-β1 and reversal of marrow fibrosis, positioning fibrocytes as an upstream cellular source of TGF-β1 driving the fibrogenic axis. (novelty: 4)
- 2026-07-16 — An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions: A Phase 3 placebo-controlled trial will test luspatercept (ActRIIB ligand trap targeting TGF-β superfamily ligands via SMAD2/3) added to concomitant JAK2 inhibitor therapy in transfusion-dependent MF, providing the first randomized late-phase test of TGF-β superfamily modulation for anemia in the JAKi-combination MF setting. (novelty: 3)
- 2026-08-25 — Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement-driven immune-stromal interactions as a therapeutic target.: Complement C3-driven reprogramming of splenic reticular cells into pro-fibrotic states is proposed as an upstream trigger feeding into TGF-β-mediated stromal remodeling, positioning complement activation as a candidate initiator of the inflammation-to-fibrosis TGF-β axis in MF. (novelty: 5)
- 2026-08-01 — Inflammatory Network Architecture Across Bone Marrow Failure: An Immune-Genetic Continuum.: Cross-BMF synthesis positions TGF-β as the mechanistic bridge coupling the shared inflammatory cytokine network (TNF-α/IFN-γ/IL-6) to fibrotic marrow remodeling, reinforcing TGF-β as the inflammation-to-fibrosis linker in MPN/MF. (novelty: 3)
- June 12-15 — Advancing Frontiers in Myeloproliferative Neoplasms - EHA 2025 Congress Review: EHA 2025 congress review positions elritercept (ActRII ligand trap) as a leading TGF-β superfamily-targeted agent advancing in MF, reinforcing TGF-β superfamily modulation as a clinically tractable axis for anemia and disease modification. (novelty: 3)
- 2026-02-05 — A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis: Early-phase trial of elritercept (an ActRII ligand trap targeting TGF-β superfamily ligands) alone or with ruxolitinib in MF extends TGF-β superfamily modulation beyond luspatercept into anemia and symptom endpoints in non-transplant MF. (novelty: 4)
- 2026-04-20 — Luspatercept in Preventing Poor Erythroid Engraftment for Hematological Malignancies With Moderate to Severe Myelofibrosis: A planned prospective multicenter RCT will test luspatercept (TGF-β superfamily ligand trap acting via SMAD2/3) for prevention of poor erythroid engraftment after allo-HSCT in moderate-to-severe myelofibrosis, providing the first randomized clinical test of TGF-β superfamily modulation to rescue post-transplant erythropoiesis in MF. (novelty: 4)
Open questions
Related
Contributing findings
Advancing Frontiers in Myeloproliferative Neoplasms - EHA 2025 Congress Review
June 12-15, 2025
novelty 3
per-area 2
mentions
New Drugs in Myelofibrosis: Incremental Progress in Symptom Management Without Disease Modification.
23-oct-2026
novelty 2
per-area 3
strengthens
Megakaryocytes in myelofibrosis: mechanisms of fibrotic niche remodeling and therapeutic implications.
29-sep-2026
novelty 2
per-area 3
strengthens
PIM1 in myeloproliferative neoplasms: potential pathogenic and therapeutic implications.
28-sep-2026
novelty 2
per-area 2
mentions
Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia.
01-sep-2026
novelty 4
per-area 3
strengthens
Dissecting Bone Marrow Fibrosis in Philadelphia-Negative Myeloproliferative Neoplasms: Multiple Roads Lead to Rome.
01-sep-2026
novelty 2
per-area 2
mentions
Spatial profiling of the spleen in mouse and human myelofibrosis reveals complement-driven immune-stromal interactions as a therapeutic target.
25-aug-2026
novelty 5
per-area 3
strengthens
Inflammatory Network Architecture Across Bone Marrow Failure: An Immune-Genetic Continuum.
01-aug-2026
novelty 3
per-area 3
strengthens
An Efficacy and Safety Study of Luspatercept (ACE-536) Versus Placebo in Subjects With Myeloproliferative Neoplasm-Associated Myelofibrosis on Concomitant JAK2 Inhibitor Therapy and Who Require Red Blood Cell Transfusions
16-jul-2026
novelty 3
per-area 3
strengthens
Hepcidin as a Molecular Hub of Iron Homeostasis: From BMP-SMAD Signaling to Therapeutic Modulation.
25-jun-2026
novelty 2
per-area 2
strengthens
A Study to Compare Elritercept to Placebo in Adults With Myelofibrosis and Anemia Who Are Taking Ruxolitinib
03-jun-2026
novelty 3
per-area 2
mentions
Luspatercept in Preventing Poor Erythroid Engraftment for Hematological Malignancies With Moderate to Severe Myelofibrosis
20-apr-2026
novelty 4
per-area 4
introduces
A Study of Elritercept Alone or Together With Ruxolitinib in Adults With Myelofibrosis
05-feb-2026
novelty 4
per-area 4
strengthens