Document Detail


Dysregulation of fatty acid synthesis and glycolysis in non-Hodgkin lymphoma.
MedLine Citation:
PMID:  22752304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The metabolic differences between B-NHL and primary human B cells are poorly understood. Among human B-cell non-Hodgkin lymphomas (B-NHL), primary effusion lymphoma (PEL) is a unique subset that is linked to infection with Kaposi's sarcoma-associated herpesvirus (KSHV). We report that the metabolic profiles of primary B cells are significantly different from that of PEL. Compared with primary B cells, both aerobic glycolysis and fatty acid synthesis (FAS) are up-regulated in PEL and other types of nonviral B-NHL. We found that aerobic glycolysis and FAS occur in a PI3K-dependent manner and appear to be interdependent. PEL overexpress the fatty acid synthesizing enzyme, FASN, and both PEL and other B-NHL were much more sensitive to the FAS inhibitor, C75, than primary B cells. Our findings suggest that FASN may be a unique candidate for molecular targeted therapy against PEL and other B-NHL.
Authors:
Aadra P Bhatt; Sarah R Jacobs; Alex J Freemerman; Liza Makowski; Jeffrey C Rathmell; Dirk P Dittmer; Blossom Damania
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-29
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-18     Completed Date:  2012-10-11     Revised Date:  2014-05-28    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11818-23     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
4-Butyrolactone / analogs & derivatives,  pharmacology
B-Lymphocytes / metabolism*
Computational Biology
Fatty Acid Synthases / antagonists & inhibitors
Fatty Acids / biosynthesis*
Glycolysis / physiology*
Humans
Immunoblotting
Lymphoma, B-Cell / metabolism*
Lymphoma, Primary Effusion / metabolism*
Metabolic Networks and Pathways / physiology*
Models, Biological
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Signal Transduction / physiology*
TOR Serine-Threonine Kinases / metabolism
Grant Support
ID/Acronym/Agency:
AA017376/AA/NIAAA NIH HHS; CA096500/CA/NCI NIH HHS; CA123350/CA/NCI NIH HHS; CA163217/CA/NCI NIH HHS; DE018304/DE/NIDCR NIH HHS; DK056350/DK/NIDDK NIH HHS; ES019472/ES/NIEHS NIH HHS; P30DK034987/DK/NIDDK NIH HHS; R01 CA123350/CA/NCI NIH HHS; R01 CA163217/CA/NCI NIH HHS; T32 AI007151/AI/NIAID NIH HHS; T32-AI007419/AI/NIAID NIH HHS; T32-CA071341/CA/NCI NIH HHS; T32-CA09156/CA/NCI NIH HHS; T32AI007151/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; 0/Fatty Acids; EC 2.3.1.85/Fatty Acid Synthases; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.1/MTOR protein, human; EC 2.7.1.1/TOR Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; OL659KIY4X/4-Butyrolactone
Comments/Corrections

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