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

181 Citations (Scopus)

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

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Lymphoma, Large B-Cell, Diffuse
B-Lymphocytes
Glutathione
B-Lymphocyte Subsets
Citric Acid Cycle
Poisons
Dermatoglyphics
Cell Survival
Fatty Acids
Carbon
Food
Genes
Neoplasms
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Cite this

Caro, P., Kishan, A. U., Norberg, E., Stanley, I. A., Chapuy, B., Ficarro, S. B., ... 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

Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma. / Caro, Pilar; Kishan, Amar U.; Norberg, Erik; Stanley, Illana A.; Chapuy, Bjoern; Ficarro, Scott B.; Polak, Klaudia; Tondera, Daniel; Gounarides, John; Yin, Hong; Zhou, Feng; Green, Michael R.; Chen, Linfeng; Monti, Stefano; Marto, Jarrod A.; Shipp, Margaret A.; Danial, Nika N.

In: Cancer Cell, Vol. 22, No. 4, 16.10.2012, p. 547-560.

Research output: Contribution to journalArticle

Caro, P, Kishan, AU, Norberg, E, Stanley, IA, Chapuy, B, Ficarro, SB, Polak, K, Tondera, D, Gounarides, J, Yin, H, Zhou, F, Green, MR, Chen, L, Monti, S, Marto, JA, Shipp, MA & Danial, NN 2012, 'Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma', Cancer Cell, vol. 22, no. 4, pp. 547-560. https://doi.org/10.1016/j.ccr.2012.08.014
Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB et al. Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma. Cancer Cell. 2012 Oct 16;22(4):547-560. https://doi.org/10.1016/j.ccr.2012.08.014
Caro, Pilar ; Kishan, Amar U. ; Norberg, Erik ; Stanley, Illana A. ; Chapuy, Bjoern ; Ficarro, Scott B. ; Polak, Klaudia ; Tondera, Daniel ; Gounarides, John ; Yin, Hong ; Zhou, Feng ; Green, Michael R. ; Chen, Linfeng ; Monti, Stefano ; Marto, Jarrod A. ; Shipp, Margaret A. ; Danial, Nika N. / Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma. In: Cancer Cell. 2012 ; Vol. 22, No. 4. pp. 547-560.
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