Differential regulation of myeloid leukemias by the bone marrow microenvironment

摘要: Like their normal hematopoietic stem cell counterparts, leukemia cells (LSC) in chronic myelogenous (CML) and acute myeloid (AML) are presumed to reside specific niches the bone marrow microenvironment (BMM)1, may be cause of relapse following chemotherapy.2 Targeting niche is a novel strategy eliminate persistent drug-resistant LSC. CD443,4 IL-65 have been implicated previously LSC niche. Transforming growth factor (TGF)-β1 released during remodeling6 plays role maintenance CML LSCs7, but for TGF-β1 from BMM has not defined. Here, we show that alteration by osteoblastic cell-specific activation parathyroid hormone (PTH) receptor8,9 attenuates BCR-ABL1-induced CML-like myeloproliferative neoplasia (MPN)10 enhances MLL-AF9-induced AML11 mouse transplantation models, possibly through opposing effects increased on respective PTH treatment caused 15-fold decrease LSCs wildtype mice with MPN, reduced engraftment immune deficient primary human cells. These results demonstrate leukemias distinct, suggest modulation feasible reduce LSC, prerequisite cure CML.