Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche

被引：427

作者：

Ye, Haobin ^{[1
,3
]}

Adane, Biniam ^{[1
]}

Khan, Nabilah ^{[1
]}

Sullivan, Timothy ^{[2
]}

Minhajuddin, Mohammad ^{[1
]}

Gasparetto, Maura ^{[1
]}

Stevens, Brett ^{[1
]}

Pei, Shanshan ^{[1
]}

Balys, Marlene ^{[4
]}

Ashton, John M. ^{[4
]}

Klemm, Dwight J. ^{[2
]}

Woolthuis, Carolien M. ^{[5
]}

Stranahan, Alec W. ^{[5
]}

Park, Christopher Y. ^{[5
]}

Jordan, Craig T. ^{[1
]}

机构：

[1] Univ Colorado, Div Hematol, Aurora, CO 80045 USA

[2] Univ Colorado, Cardiovasc Pulm Res Lab, Aurora, CO 80045 USA

[3] Univ Rochester, Med Ctr, Dept Pathol, Rochester, NY 14642 USA

[4] Univ Rochester, Med Ctr, Funct Genom Ctr, Rochester, NY 14642 USA

[5] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

来源：

CELL STEM CELL | 2016年 / 19卷 / 01期

关键词：

HEMATOPOIETIC STEM; INSULIN-RESISTANCE; MURINE MODEL; IN-VIVO; MECHANISMS; INHIBITION; TRANSPLANTATION; INFLAMMATION; CONTRIBUTES; PROGENITOR;

D O I：

10.1016/j.stem.2016.06.001

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT. GAT lipolysis fuels fatty acid oxidation in LSCs, especially within a subpopulation expressing the fatty acid transporter CD36. CD36(+) LSCs have unique metabolic properties, are strikingly enriched in AT, and are protected from chemotherapy by the GAT microenvironment. CD36 also marks a fraction of human blast crisis CML and acute myeloid leukemia (AML) cells with similar biological properties. These findings suggest striking interplay between leukemic cells and AT to create a unique microenvironment that supports the metabolic demands and survival of a distinct LSC subpopulation.

引用

页码：23 / 37

页数：15

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