CCR2 monocyte trafficking in MPN fibrosis

Current understanding

C-C chemokine receptor 2 (CCR2) is expressed on inflammatory monocytes and fibrocyte precursors that traffic to the bone marrow stroma, where they are hypothesized to contribute to fibrotic remodeling in myeloproliferative neoplasms. Preclinical and first-in-human proof-of-concept work suggests CCR2+ cells are detectable both by peripheral flow cytometry and by 68Ga-DOTA-ECL1i PET-CT, raising the possibility that CCR2 is a tractable cellular biomarker linking chronic inflammation to marrow fibrogenesis. The mechanistic role of CCR2-CCL2 signaling in MPN megakaryocyte-stromal crosstalk remains to be formally established.

Evidence log

• 2026-09-01 — Fibrocytes drive JAK2V617F-mutated myelofibrosis: pitavastatin reverses marrow fibrosis and anemia.: Preclinical JAK2V617F MF work substantiates the CCR2-monocyte-to-fibrocyte pipeline as mechanistically fibrogenic by showing monocyte-derived fibrocytes produce most marrow collagen and that pitavastatin-induced fibrocyte depletion reverses fibrosis and anemia. (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): Axatilimab + ruxolitinib phase I/II adds a second monocyte/macrophage-directed strategy (CSF1R survival axis) alongside CCR2 trafficking as targetable arms of the inflammatory-monocyte contribution to MF/CMML. (novelty: 3)
• 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: Phase Ib/II trial of axatilimab (anti-CSF-1R) ± azacitidine in advanced MPN, MPN/MDS overlap, and high-risk CMML introduces a complementary macrophage-directed axis to the CCR2 monocyte-trafficking model, targeting CSF-1R-dependent macrophage survival/differentiation rather than CCL2-CCR2-driven recruitment. (novelty: 4)

Open questions

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