Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts

摘要: The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematologic cancers. We hypothesized that osteoblasts, components the involved in hematopoietic stem cell (HSC) function, influence fate leukemic blasts. show osteoblast numbers decrease by 55% myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion osteoblasts mouse models increased circulating blasts tumor engraftment spleen leading higher burden shorter survival. Myelopoiesis was coupled with reduction B lymphopoiesis compromised erythropoiesis, suggesting lineage/progression altered. Treatment mice lymphoblastic pharmacologic inhibitor synthesis duodenal serotonin, hormone suppressing numbers, inhibited loss osteoblasts. Maintenance pool restored normal reduced burden, prolonged Leukemia prevention attributable maintenance because inhibition serotonin receptors alone did not affect progression. These results suggest play fundamental role propagating may be therapeutic target induce hostility