CSF-1R signaling and macrophage axis in MPN
Current understanding
Colony-stimulating factor 1 receptor (CSF-1R) is expressed on monocytes and tissue macrophages and drives their differentiation, survival, and trafficking; in myeloid malignancies including advanced MPN, MPN/MDS overlap, and CMML, CSF-1R-dependent macrophages are hypothesized to support a pro-inflammatory, pro-fibrotic marrow niche and to enable clonal persistence. Axatilimab, an anti-CSF-1R monoclonal antibody, is being clinically evaluated alone or with azacitidine as a first-in-class macrophage-directed therapy in these indications, but mechanistic evidence in MPN remains early (trial-early). The relationship of the CSF-1R/macrophage axis to CCR2-driven monocyte recruitment, JAK-STAT-driven cytokine production, and bone marrow fibrosis remains to be formally established.
Evidence log
- 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): cross-connection with csf1r-macrophage-signaling-mpn: Two overlapping CSF1R/macrophage pages both accumulate axatilimab clinical trial evidence; the ruxolitinib-combination arm extends the macrophage-axis hypothesis into JAK-inhibitor-treated MF and CMML. (novelty: 3)
- 2026-06-16 — Lysozyme-Associated Nephropathy in Myeloid Neoplasms: A Clinicopathological and Mass Spectrometric Study of Two Cases.: cross-connection with lysozyme-associated-nephropathy-mechanism: Monocyte/macrophage expansion under CSF-1R signaling in MPN/CMML is the likely cellular source of the lysozyme overload causing LyN, linking the macrophage axis to renal proximal tubule injury. (novelty: 4)
- 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 ccr2-monocyte-trafficking-mpn: CSF-1R and CCR2 represent two complementary mechanisms governing the monocyte-macrophage compartment in MPN: CCR2 mediates recruitment of inflammatory monocytes/fibrocyte precursors to marrow, while CSF-1R sustains their differentiation and survival as tissue macrophages — jointly shaping the pro-fibrotic niche. (novelty: 4)