Aging of Bone Marrow Microenvironment Promotes Myeloid Bias of Hematopoietic Progenitors and Is a Target in Age Related Myeloproliferative Neoplasms

Background: BM HSC accumulate during aging but are functionally impaired; however, it remains debated whether this aging results from HSC-intrinsic and/or-extrinsic mechanisms. Myeloid malignancies are more frequent in the elderly, but whether the aged microenvironment predisposes to these malignancies is unclear. Myeloid-biased HSC and especially platelet-primed HSC expand in aged mice. However, both platelet-primed and unprimed old HSCs exhibit myeloid bias, possibly suggesting a microenvironmental participation. Moreover, some hallmarks of murine hematopoietic aging (like increased platelets) are present in premature aging (Hutchinson-Gilford progeria syndrome, HGPS) and are exacerbated in age-related myeloproliferative neoplasms (MPN), where we found that niche heterogeneity can influence disease progression (ASH abstract ID 113495). Given that aging increases myelopoiesis in …