Functional Niche Competition Between Normal Hematopoietic Stem and Progenitor Cells and Myeloid Leukemia Cells.

摘要: Hematopoietic stem and progenitor cells (HSPCs) reside in a specialized niche that regulates their proliferative capacity fate. There is increasing evidence for similar roles of marrow niches on controlling the behavior leukemic cells; however, whether normal hematopoietic cell (HSC) or functionally compete same unclear. We used mixed lineage leukemia-AF9 (MLL-AF9) murine acute myeloid leukemia (AML) competitive repopulation model to investigate HSPC niches. Irradiated recipient mice were transplanted with fixed numbers MLL-AF9 doses syngeneic whole bone (WBM) purified (LSK). Survival was significantly increased progression delayed proportional WBM LSK multiple independent experiments, all studied above threshold rapid complete reconstitution absence leukemia. Confocal microscopy demonstrated nests either but not both adjacent endosteum. Early following transplantation, from animals receiving lower cycling more actively than those higher doses. These results suggest AML functional niche. Manipulation could impact response antileukemic therapies, outcome, informing approaches dose context transplantation.