NDLI: Adipocytes Cause Leukemia Cell Resistance to L-Asparaginase via Release of Glutamine

Content Provider	PubMed Central
Author	Ehsanipour, Ehsan A. Sheng, Xia Behan, James W. Wang, Xingchao Butturini, Anna Avramis, Vassilios I. Mittelman, Steven D.
Abstract	Obesity is a significant risk factor for cancer. A link between obesity and a childhood cancer has been identified: obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) had a 50% greater risk of relapse than their lean counterparts. L-asparaginase (ASNase) is a first-line therapy for ALL that breaks down asparagine and glutamine, exploiting the fact that ALL cells are more dependent on these amino acids than other cells. In the present study, we investigated whether adipocytes, which produce significant quantities of glutamine, may counteract the effects of ASNase. In children being treated for high-risk ALL, obesity was not associated with altered plasma levels of asparagine or glutamine. However, glutamine synthetase was markedly increased in bone marrow adipocytes after induction chemotherapy. Obesity substantially impaired ASNase efficacy in mice transplanted with syngeneic ALL cells, and, like in humans, without affecting plasma asparagine or glutamine levels. In co-culture, adipocytes inhibited leukemic cell cytotoxicity induced by ASNase, and this protection was dependent on glutamine secretion. These findings suggest that adipocytes work in conjunction with other cells of the leukemia microenvironment to protect leukemia cells during ASNase treatment.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-12-4402
Ending Page	3006
Page Count	9
Starting Page	2998
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	10
Volume Number	73
Language	English
Publisher Date	2013-05-15
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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