Novel selective regulation of hematopoietic progenitor self-renewal, survival and proliferation by estrogens has therapeutic potential in myeloproliferative neoplasms

ABSTRACT: Estrogens are potential regulators of the hematopoietic stem cell (HSC) niche and have effects on mature hematopoietic cells; however, whether estrogen signaling directly regulates normal and malignant HSC remains unclear. We demonstrate differential expression and specific roles of estrogen receptors (ER) in hematopoietic progenitors. ERa activation in short-term HSC and multipotent progenitors induced apoptosis. In contrast, the selective ER modulator (SERM) tamoxifen induced proliferation of quiescent long-term HSC, altered their self-renewal signature and compromised hematopoietic reconstitution following myelotoxic stress. Treatment with tamoxifen alone abolished hematopoietic progenitor expansion induced by JAK2V617F by restoring normal levels of apoptosis, blocked JAK2V617F-induced

ORGANISM(S): Mus musculus

SUBMITTER: Simón Méndez-Ferrer 

PROVIDER: E-GEOD-62621 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress