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Blood. 2015 Mar 26;125(13):2120-30. doi: 10.1182/blood-2014-08-594408. Epub 2015 Jan 28.

AML cells have low spare reserve capacity in their respiratory chain that renders them susceptible to oxidative metabolic stress.

Author information

1
Princess Margaret Cancer Centre, Ontario Cancer Institute, Toronto, ON, Canada;
2
Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, ON, Canada; and.
3
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
4
Princess Margaret Cancer Centre, Ontario Cancer Institute, Toronto, ON, Canada; Division of Stem Cell and Developmental Biology, Campbell Family Institute for Cancer Research/Ontario Cancer Institute, Toronto, ON, Canada; and.

Abstract

Mitochondrial respiration is a crucial component of cellular metabolism that can become dysregulated in cancer. Compared with normal hematopoietic cells, acute myeloid leukemia (AML) cells and patient samples have higher mitochondrial mass, without a concomitant increase in respiratory chain complex activity. Hence these cells have a lower spare reserve capacity in the respiratory chain and are more susceptible to oxidative stress. We therefore tested the effects of increasing the electron flux through the respiratory chain as a strategy to induce oxidative stress and cell death preferentially in AML cells. Treatment with the fatty acid palmitate induced oxidative stress and cell death in AML cells, and it suppressed tumor burden in leukemic cell lines and primary patient sample xenografts in the absence of overt toxicity to normal cells and organs. These data highlight a unique metabolic vulnerability in AML, and identify a new therapeutic strategy that targets abnormal oxidative metabolism in this malignancy.

PMID:
25631767
PMCID:
PMC4375109
DOI:
10.1182/blood-2014-08-594408
[Indexed for MEDLINE]
Free PMC Article

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