Energy metabolism is co-determined by genetic variants in chronic lymphocytic leukemia and influences drug sensitivity

Haematologica
Junyan LuWolfgang Huber

Abstract

Chronic lymphocytic leukemia cells have an altered energy metabolism compared to normal B cells. While there is a growing understanding of the molecular heterogeneity of the disease, the extent of metabolic heterogeneity and its relation to molecular heterogeneity has not been systematically studied. Here, we assessed 11 bioenergetic features, primarily reflecting cell oxidative phosphorylation and glycolytic activity, in leukemic cells from 140 chronic lymphocytic leukemia patients using metabolic flux analysis. We examined these bioenergetic features for relationships with molecular profiles (including genetic aberrations, transcriptome and methylome profiles) of the tumors, their ex vivo responses to a panel of 63 compounds, and with clinical data. We observed that leukemic cells with mutated immunoglobulin variable heavy-chain show significantly lower glycolytic activity than cells with unmutated immunoglobulin variable heavy-chain. Accordingly, several key glycolytic genes (PFKP, PGAM1 and PGK1) were found to be down-regulated in samples harboring mutated immunoglobulin variable heavy-chain. In addition, 8q24 copy number gains, 8p12 deletions, 13q14 deletions and ATM mutations were identified as determinants of cellular re...Continue Reading

Citations

Dec 1, 2020·Frontiers in Oncology·Martin BöttcherDimitrios Mougiakakos
May 2, 2021·Journal for Immunotherapy of Cancer·Martin BöttcherDimitrios Mougiakakos
Jun 22, 2021·Cancer Biomarkers : Section a of Disease Markers·Viktória TemesfőiZsuzsanna Faust
Aug 8, 2021·International Journal of Molecular Sciences·Aikaterini Poulaki, Stavroula Giannouli
Dec 17, 2021·Blood·Visith Thongboonkerd
Jul 1, 2021·Blood·Fabienne Meier-AbtThorsten Zenz

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Datasets Mentioned

BETA
GSE49695
GSE30105

Software Mentioned

R package
R Shiny
R
Wave Desktop

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