Unknown

Dataset Information

0

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.

SUBMITTER: Ye H 

PROVIDER: S-EPMC4938766 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 fue  ...[more]

Similar Datasets

| S-EPMC5824652 | biostudies-literature
| S-EPMC6664146 | biostudies-literature
| S-SCDT-EMBOR-2018-47546-T | biostudies-other
| S-EPMC6607014 | biostudies-literature
| S-EPMC3965366 | biostudies-literature
| S-EPMC5120333 | biostudies-literature
| S-EPMC4254082 | biostudies-literature
2018-04-01 | GSE109574 | GEO
| S-EPMC4172227 | biostudies-literature
| S-EPMC4395137 | biostudies-literature