biostudies-literatureHanoun MNIDDK NIH HHSNHLBI NIH HHSNCI NIH HHSNIGMS NIH HHS365-375https://www.ebi.ac.uk/biostudies/studies/S-EPMC4156919biostudies-literatureUnknown15(3)Perivascular mesenchymal stem and progenitor cells (MSPCs) are critical for forming a healthy hematopoietic stem cell (HSC) niche. However, the interactions and influence of acute myelogenous leukemia (AML) stem cells with the microenvironment remain largely unexplored. We have unexpectedly found that neuropathy of the sympathetic nervous system (SNS) promotes leukemic bone marrow infiltration in an MLL-AF9 AML model. Development of AML disrupts SNS nerves and the quiescence of Nestin(+) niche cells, leading to an expansion of phenotypic MSPCs primed for osteoblastic differentiation at the expense of HSC-maintaining NG2(+) periarteriolar niche cells. Adrenergic signaling promoting leukemogenesis is transduced by the β2, but not β3, adrenergic receptor expressed on stromal cells of leukemicCell stem cellAcute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche.PMC4156919GM007491DK056638HL097819P30 CA008748CA66996R01 CA140575HL116340R01 DK056638CA140575T32 GM007491P30 CA013330P01 CA066996R01 HL116340R01 HL097819Armstrong SAPinho SZhang DFrenette PSHanoun MPierce HKunisaki YLacombe JMizoguchi TDuhrsen UfalseAcute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche.Perivascular mesenchymal stem and progenitor cells (MSPCs) are critical for forming a healthy hematopoietic stem cell (HSC) niche. However, the interactions and influence of acute myelogenous leukemia (AML) stem cells with the microenvironment remain largely unexplored. We have unexpectedly found that neuropathy of the sympathetic nervous system (SNS) promotes leukemic bone marrow infiltration in an MLL-AF9 AML model. Development of AML disrupts SNS nerves and the quiescence of Nestin(+) niche cells, leading to an expansion of phenotypic MSPCs primed for osteoblastic differentiation at the expense of HSC-maintaining NG2(+) periarteriolar niche cells. Adrenergic signaling promoting leukemogenesis is transduced by the β2, but not β3, adrenergic receptor expressed on stromal cells of leukemic2014-01-01T00:00:00Z2014 Sep2025-04-19T08:54:34.632Z2019-03-27T01:35:20ZS-EPMC41569192501772210.1016/j.stem.2014.06.020