With a growing aged population, there is an imminent need to develop new therapeutic strategies to ameliorate disorders of hematopoietic aging, including clonal hematopoiesis and myelodysplastic syndrome (MDS). Cell-intrinsic dysregulation of innate immune- and inflammatory-related pathways as well as systemic inflammation have been implicated in hematopoietic defects associated with aging, clonal hematopoiesis, and MDS. Here, we review and discuss the role of dysregulated innate immune and inflammatory signaling that contribute to the competitive advantage and clonal dominance of preleukemic and MDS-derived hematopoietic cells. We also propose how emerging concepts will further reveal critical biology and novel therapeutic opportunities.
Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS
Disclosures: J.J. Trowbridge reported grants from H3 Biomedicine and non-financial support from Navitor Pharmaceuticals, Inc outside the submitted work; in addition, J.J. Trowbridge had a patent to US-7850960-B2 Methods for regulation of stem cells with royalties paid by Fate Therapeutics. D.T. Starczynowski reported personal fees from Kurome Therapeutics, Kymera Therapeutics, and Captor Therapeutics, and grants from Tolera Therapeutics outside the submitted work. Additionally, D.T. Starczynowski serves on the scientific advisory board and has equity in Kurome Therapeutics.
- Views Icon Views
- Share Icon Share
- Search Site
Jennifer J. Trowbridge, Daniel T. Starczynowski; Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS. J Exp Med 5 July 2021; 218 (7): e20201544. doi: https://doi.org/10.1084/jem.20201544
Download citation file: