Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche Journal Article
| Authors: | Ye, H.; Adane, B.; Khan, N.; Minhajuddin, M.; Gasparetto, M.; Stevens, B.; Pei, S.; Balys, M.; Ashton, J. M.; Klemm, D. J.; Woolthuis, C. M.; Stranahan, A. W.; Park, C. Y.; Jordan, C. T. |
| Article Title: | Leukemic stem cells evade chemotherapy by metabolic adaptation to an adipose tissue niche |
| Abstract: | 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. © 2016 Elsevier Inc. |
| Journal Title: | Cell Stem Cell |
| Volume: | 19 |
| Issue: | 1 |
| ISSN: | 1934-5909 |
| Publisher: | Cell Press |
| Date Published: | 2016-07-07 |
| Start Page: | 23 |
| End Page: | 37 |
| Language: | English |
| DOI: | 10.1016/j.stem.2016.06.001 |
| PROVIDER: | scopus |
| PMCID: | PMC4938766 |
| PUBMED: | 27374788 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 February 2017 -- Source: Scopus |
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