Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma.
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.
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Pilar
P
Caro
Amar U
AU
Kishan
Erik
E
Norberg
Illana A
IA
Stanley
Bjoern
B
Chapuy
Scott B
SB
Ficarro
Klaudia
K
Polak
Daniel
D
Tondera
John
J
Gounarides
Hong
H
Yin
Feng
F
Zhou
Michael R
MR
Green
Linfeng
L
Chen
Stefano
S
Monti
Jarrod A
JA
Marto
Margaret A
MA
Shipp
Nika N
NN
Danial
D002470:Cell Survival; D002952:Citric Acid Cycle; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D020543:Proteome; D011947:Receptors, Antigen, B-Cell / Q000502:physiology
D005227:Fatty Acids; D020543:Proteome; D011947:Receptors, Antigen, B-Cell