Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche Journal Article


Authors: Hanoun, M.; Zhang, D. C.; Mizoguchi, T.; Pinho, S.; Pierce, H.; Kunisaki, Y.; Lacombe, J.; Armstrong, S. A.; Duḧrsen, U.; Frenette, P. S.
Article Title: Acute myelogenous leukemia-induced sympathetic neuropathy promotes malignancy in an altered hematopoietic stem cell niche
Abstract: 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 beta 2, but not beta 3, adrenergic receptor expressed on stromal cells of leukemic bone marrow. These results indicate that sympathetic neuropathy may represent a mechanism for the malignancy in order to co-opt the microenvironment and suggest separate mesenchymal niche activities for malignant and healthy hematopoietic stem cells in the bone marrow.
Keywords: angiogenesis; regeneration; microenvironment; model; progenitor cells; nervous-system; maintenance; acute myeloid-leukemia; bone-marrow niche; increased; mll-af9
Journal Title: Cell Stem Cell
Volume: 15
Issue: 3
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2014-09-04
Start Page: 365
End Page: 375
Language: English
ACCESSION: WOS:000341441600015
DOI: 10.1016/j.stem.2014.06.020
PROVIDER: wos
PMCID: PMC4156919
PUBMED: 25017722
Notes: Article -- Source: Wos
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  1. Scott Allen Armstrong
    108 Armstrong