@article{c5bcb83aa1734298aca1e8bfd38d531a,
title = "Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma",
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.",
author = "Pilar Caro and Kishan, {Amar U.} and Erik Norberg and Stanley, {Illana A.} and Bjoern Chapuy and Ficarro, {Scott B.} and Klaudia Polak and Daniel Tondera and John Gounarides and Hong Yin and Feng Zhou and Green, {Michael R.} and Linfeng Chen and Stefano Monti and Marto, {Jarrod A.} and Shipp, {Margaret A.} and Danial, {Nika N.}",
note = "Funding Information: We thank Eric Smith for manuscript preparation. We gratefully acknowledge George Rogers, Martin Brand, David Ferrick, Min Wu, and Orian Shirihai for advice on respirometry; Wei Jiang and Frank Cook for assistance with LC-MS/MS and GC/MS; and Georg Lenz and Frank Stegmeier for HBL-1 and U2932 DLBCL cell lines. A.U.K. was supported by the Alexandra Jane Miliotis Fellowship in Pediatric Oncology, the IDEAˆ2 Program Grant from the Harvard-MIT Division of Health Sciences and Technology, and a Medical Student Research Training Fellowship from the Howard Hughes Medical Institute. E.N. was supported by a postdoctoral fellowship from the Swedish Research Council. This work was supported in part by funding from the Novartis Institutes for Biomedical Research (N.N.D.), National Institutes of Health Grant PO1 CA092625 (M.A.S.), and the German Research Foundation DFG Ch 735/1-1 (B.C.). The authors acknowledge generous support provided through the Dana-Farber Cancer Institute Strategic Research Initiative (to J.A.M.). N.N.D. is a recipient of the Burroughs Welcome Fund Career Award in Biomedical Sciences and a consultant for the Novartis Institutes for Biomedical Research. ",
year = "2012",
month = oct,
day = "16",
doi = "10.1016/j.ccr.2012.08.014",
language = "English (US)",
volume = "22",
pages = "547--560",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "4",
}