Acute Myelogenous Leukemia-Induced Sympathetic Neuropathy Promotes Malignancy in an Altered Hematopoietic Stem Cell Niche

被引：333

作者：

Hanoun, Maher ^{[1
,2
]}

Zhang, Dachuan ^{[1
,2
]}

Mizoguchi, Toshihide ^{[1
,2
]}

Pinho, Sandra ^{[1
,2
]}

Pierce, Halley ^{[1
,2
]}

Kunisaki, Yuya ^{[1
,2
]}

Lacombe, Julie ^{[1
,2
]}

Armstrong, Scott A. ^{[4
]}

Duehrsen, Ulrich ^{[5
]}

Frenette, Paul S. ^{[1
,2
,3
]}

机构：

[1] Albert Einstein Coll Med, Ruth L & David S Gottesman Inst Stem Cell & Regen, Bronx, NY 10461 USA

[2] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA

[3] Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA

[4] Mem Sloan Kettering Canc Ctr, Mem Hosp Res Labs, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[5] Univ Duisburg Essen, Univ Hosp, Dept Hematol, D-45122 Essen, Germany

来源：

CELL STEM CELL | 2014年 / 15卷 / 03期

基金：

美国国家卫生研究院;

关键词：

ACUTE MYELOID-LEUKEMIA; BONE-MARROW NICHE; NERVOUS-SYSTEM; INCREASED ANGIOGENESIS; PROGENITOR CELLS; MICROENVIRONMENT; REGENERATION; MAINTENANCE; MLL-AF9; MODEL;

D O I：

10.1016/j.stem.2014.06.020

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：365 / 375

页数：11

共 36 条

[1]

Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes [J].