Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma

Pilar Caro, Amar U. Kishan, Erik Norberg, Illana A. Stanley, Bjoern Chapuy, Scott B. Ficarro, Klaudia Polak, Daniel Tondera, John Gounarides, Hong Yin, Feng Zhou, Michael R. Green, Linfeng Chen, Stefano Monti, Jarrod A. Marto, Margaret A. Shipp, Nika N. Danial

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Molecular signatures have identified several subsets of diffuse large B cell lymphoma (DLBCL) and rational targets within the B cell receptor (BCR) signaling axis. The OxPhos-DLBCL subset, which harbors the signature of genes involved in mitochondrial metabolism, is insensitive to inhibition of BCR survival signaling but is functionally undefined. We show that, compared with BCR-DLBCLs, OxPhos-DLBCLs display enhanced mitochondrial energy transduction, greater incorporation of nutrient-derived carbons into the tricarboxylic acid cycle, and increased glutathione levels. Moreover, perturbation of the fatty acid oxidation program and glutathione synthesis proved selectively toxic to this tumor subset. Our analysis provides evidence for distinct metabolic fingerprints and associated survival mechanisms in DLBCL and may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)547-560
Number of pages14
JournalCancer Cell
Volume22
Issue number4
DOIs
StatePublished - Oct 16 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Caro, P., Kishan, A. U., Norberg, E., Stanley, I. A., Chapuy, B., Ficarro, S. B., Polak, K., Tondera, D., Gounarides, J., Yin, H., Zhou, F., Green, M. R., Chen, L., Monti, S., Marto, J. A., Shipp, M. A., & Danial, N. N. (2012). Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma. Cancer Cell, 22(4), 547-560. https://doi.org/10.1016/j.ccr.2012.08.014