Common Antihistamine Reveals New Pathway Regulating Hematopoiesis
Case CCC investigators have identified mast cell-derived histamine as a previously unrecognized suppressor of hematopoiesis, revealing a new pathway that could potentially be targeted to improve blood-cell recovery following transplantation or marrow injury.
In a preclinical model, mast cell deficiency expanded hematopoietic stem and progenitor cell (HSPC) populations, increased HSC quiescence, and enhanced resistance to myeloablative chemotherapy. Transplantation studies showed that these effects were driven primarily by remodeling of the bone marrow niche, rather than HSC-intrinsic changes.
The team traced the effect to histamine signaling. Blocking H1R with the widely used FDA-approved antihistamine cetirizine expanded HSPCs and enhanced hematopoietic recovery following transplantation in this model.
The work defines a novel H1R-dependent mast cell–histamine–bone marrow niche axis, distinct from previously described H2R-mediated regulation of HSCs.
Supporting its translational potential, a retrospective analysis of human electronic health records found antihistamine use was associated with a greater incidence of elevated white blood cell counts. The findings raise the possibility of repurposing H1R antagonists to enhance hematopoietic regeneration, although clinical investigation is needed.
Published in Experimental Hematology, the study reflects cross-consortium collaboration among investigators at Case Western Reserve University, University Hospitals Seidman Cancer Center and Cleveland Clinic, including senior author Amar Desai, PhD, and Stanton L. Gerson, MD, members of the Immune Oncology Program; and Sanford Markowitz, MD, PhD, and Rong Xu, PhD, members of the Cancer Genomics and Epigenomics Program.
The research was supported in part by Case Comprehensive Cancer Center shared resources funded through the NCI Cancer Center Support Grant (P30CA043703). The information does not necessarily reflect the opinion of the NIH.