Bone marrow fibrosis

Current understanding

Reticulin and collagen fibrosis in the marrow stroma is the defining feature of PMF and a feared progression endpoint for ET and PV.

Evidence log

• 2026-09-01 — Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia.: Preclinical JAK2V617F MF work reframes the cellular origin of marrow collagen away from megakaryocyte-driven myofibroblasts toward monocyte-derived fibrocytes, with pitavastatin reversing fibrosis and anemia via fibrocyte inhibition and TGF-β1 reduction. (novelty: 4)
• 2026-07-15 — Phase I/II Clinical Trial of Axatilimab, a CSF1R Monoclonal Antibody, in Combination With Ruxolitinib as Therapy for Patients With Myelofibrosis (MF) and Chronic Myelomonocytic Leukemia (CMML): Early-phase axatilimab + ruxolitinib trial in MF/CMML positions CSF1R-directed macrophage depletion as a candidate anti-fibrotic partner to JAK inhibition, though the abstract reports only dose-finding objectives without fibrosis readouts. (novelty: 3)
• 2026-09-01 — Genomic Evolution of Myeloproliferative Neoplasms and Therapy-Associated Mutagenesis.: Longitudinal WGS suggests fibrotic progression, like leukemic transformation, is genomically pre-encoded in clonal architecture years before overt fibrosis, linking marrow remodeling endpoints to specific evolutionary routes (notably stepwise high-molecular-risk co-mutation accrual). (novelty: 4)
• 2026-07-09 — Glutamate accumulation in myelofibrosis microenvironment rewires mesenchymal stromal cells metabolic and epigenetic profiles.: Preclinical work identifies a glutamate–mGluR5–fumarate axis in stromal MSCs as a novel metabolic-epigenetic driver of marrow fibrosis, pharmacologically attenuated by mGluR5 blockade. (novelty: 5)
• 2026-08-03 — Spatially resolved transcriptomic profiling of myelofibrosis spleen reveals compartment specific niche programs.: In MF spleen, perivascular niches display a fibro-remodeling transcriptional program with retained CXCL12 cues, implicating extramedullary perivascular stroma as an anatomically distinct site of MPN-associated fibrogenesis parallel to marrow reticulin fibrosis. (novelty: 4)
• 2025-05-13 — Development of an automated artificial intelligence-based tool for reticulin fibrosis assessment in bone marrow biopsies.: An InceptionV3-based fully convolutional network trained on whole-slide images grades reticulin fibrosis MF0–MF3 with Cohen’s κ=0.831 vs expert hematopathologists, offering a standardized digital-pathology readout that mitigates inter-observer variability in MF grading. (novelty: 3)
• 2026-08-06 — Collagen Turnover Is Associated with Disease Severity, Bone Marrow Fibrosis, and theVariant Allele Frequency in Myeloproliferative Neoplasms.: Serum PRO-C3 (type III collagen formation neoepitope) is elevated in MPN vs healthy controls, highest in PMF, and correlates with bone-marrow fibrosis grade, supporting circulating collagen-turnover fragments as non-invasive readouts of the fibrotic marrow ECM. (novelty: 3)
• 2026-08-03 — Non-invasive multiparametric characterization of essential thrombocythemia, premyelofibrosis, and overt myelofibrosis.: Non-invasive panel of inflammatory, immune-activation, and matrix-regulator markers discriminates overt PMF from ET and partially separates prefibrotic MF, supporting a measurable circulating signature of the fibrotic continuum without marrow biopsy. (novelty: 3)
• 2026-08-18 — Immune and cytokine landscape differs between cytopenic and proliferative phenotypes in primary myelofibrosis.: Cytopenic PMF, despite similar fibrotic marrow morphology, exhibits distinct NF-κB inflammatory activation and IL-8/G-CSF elevation compared to proliferative PMF, suggesting the fibrotic microenvironment coexists with divergent inflammatory programs that shape clinical aggressiveness. (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.: Preclinical spatial profiling links splenic complement C3 activity to bone marrow fibrosis: C3 inhibition in myelofibrosis models reduces both extramedullary splenic fibrotic niches and marrow reticulin fibrosis, implicating complement as an upstream fibrogenic axis. (novelty: 5)
• 2026-08-01 — Inflammatory Network Architecture Across Bone Marrow Failure: An Immune-Genetic Continuum.: Integrative review frames MPN/MF fibrosis as the fibrotic pole of a shared BMF inflammatory-genetic continuum, with TGF-β transducing conserved TNF-α/IFN-γ/IL-6 inflammation into stromal remodeling. (novelty: 3)
• June 12-15 — Advancing Frontiers in Myeloproliferative Neoplasms - EHA 2025 Congress Review: EHA 2025 review summarizes MANIFEST-2 phase III data for pelabresib + ruxolitinib and elritercept in MF, framing BET inhibition and TGF-β superfamily ligand trapping as converging strategies to modify the fibrotic marrow microenvironment. (novelty: 3)
• 2026-06-05 — The impact of novel bet inhibitors on the treatment armamentarium of Myelofibrosis.: Synthesis review identifies fibrosis-relevant transcriptional programs (TGF-β-responsive, megakaryocyte-stromal) as a key target of BET inhibition, with pelabresib + ruxolitinib trials reporting bone marrow fibrosis grade improvements as an anti-fibrotic readout. (novelty: 3)
• 2026-05-26 — JAK2V617F Mutated Endothelium Has a Stem Cell Potential in Primary Myelofibrosis: a New Disease Ontogenesis for Chronic Myeloproliferative Disorders: cross-connection with jak2v617f-hemogenic-endothelium-cell-of-origin: Mutated endothelium-as-stem-cell model offers an alternative source for the fibrosis-driving clonal megakaryocyte and stromal progeny in PMF. (novelty: 5)
• 2026-03-13 — Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia: cross-connection with csf1r-macrophage-axis-mpn: CSF-1R-dependent macrophages are candidate effectors of marrow fibrogenesis; axatilimab’s clinical development in advanced MPN tests whether macrophage blockade translates into anti-fibrotic activity. (novelty: 4)
• 2026-02-04 — 18F-FAPI PET/MRI Imaging in Myelofibrosis: a Prospective Observational Study.: A prospective multi-center study evaluates 18F-FAPI PET/MRI (targeting fibroblast activation protein) versus 18F-FDG PET/CT for non-invasive systemic fibrosis assessment in MF, correlating imaging with marrow biopsy and prognosis and implicating activated FAP+ fibroblasts as an imageable driver of MPN fibrosis. (novelty: 4)
• 2026-02-04 — Treating Anemia in Myelofibrosis With Repurposed Drugs (Nelfinavir) That Restore Iron Delivery to the Bone Marrow: An early-phase nelfinavir trial in MF includes serum fibrosis biomarker reduction as a co-readout alongside anemia improvement, hypothesizing that restoring marrow iron delivery may concomitantly attenuate fibrogenic signaling. (novelty: 4)
• 2026-04-20 — Luspatercept in Preventing Poor Erythroid Engraftment for Hematological Malignancies With Moderate to Severe Myelofibrosis: A planned RCT of luspatercept post-allo-HSCT in moderate-to-severe myelofibrosis links residual fibrotic marrow microenvironment to impaired erythroid engraftment, implicating TGF-β superfamily signaling as a modifiable contributor to fibrosis-associated post-transplant cytopenias. (novelty: 4)
• 2026-02-18 — A New Diagnostic Algorithm to Non-invasively Track Fibrotic Changes in Myeloproliferative Neoplasms Based on C-C Chemokine Receptor 2 Detection. From Flow Cytometry to the Development of Targeted Positron Emission Tomography Molecular Imaging. Pre-clinical Studies and First In-human Proof of Concept: First-in-human proof-of-concept study proposes CCR2+ cell detection (flow cytometry plus 68Ga-DOTA-ECL1i PET-CT) as a non-invasive biomarker of marrow fibrosis, implicating CCR2-expressing inflammatory/fibrocytic cells as a measurable contributor to MPN fibrotic progression. (novelty: 4)
• 2026-04-28 — A Randomized Study of ASTX727 With or Without Iadademstat in Advanced Myeloproliferative Neoplasms (MPNs): A randomized phase II of ASTX727 ± iadademstat targets accelerated/blast-phase Ph-negative MPN, an advanced disease state typically arising from fibrotic MPN progression, though fibrosis modulation is not a primary readout. (novelty: 4)
• 2026-02-06 — Pacritinib For Bone Marrow Fibrosis In Patients With Myelofibrosis Who Have Thrombocytopenia: PACRIMYEL trial uses MRI-based bone marrow fibrosis quantification as a novel endpoint to test whether dual JAK2/IRAK1 inhibition by pacritinib reduces fibrosis in thrombocytopenic MF patients. (novelty: 4)
• 2026-03-23 — Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis: Phase 3 navitoclax + ruxolitinib trial includes spleen volume reduction as the primary endpoint and is positioned to test whether dual BCL-2/BCL-XL + JAK inhibition modifies bone marrow fibrosis biology in adult MF. (novelty: 3)
• 2026-04-27 — Liver and Spleen Point Shear-Wave Elastography in Newly Diagnosed BCR::ABL1-Negative Myeloproliferative Neoplasms: Associations with Hematologic Parameters and Bone Marrow Fibrosis Grade - A Prospective Cross-Sectional Study.: Hepatic stiffness on point shear-wave elastography modestly correlates with bone marrow fibrosis grade at MPN diagnosis, suggesting non-invasive imaging may partially reflect marrow fibrotic burden. (novelty: 3)
• 2026-04-27 — Clinical Impact of Next-Generation Sequencing-Detected Mutations on Thrombotic Events in Myeloproliferative Neoplasms.: ASXL1 and splicing factor mutations were associated with bone marrow fibrosis in a 91-patient classical MPN NGS cohort. (novelty: 3)

Open questions

Related mechanisms

• megakaryocyte-dysfunction
• inflammatory-cytokine-signaling