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. 2018 Jan 24;8(1):13.
doi: 10.1038/s41408-017-0039-2.

Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and differential response to GLS1 and glucose metabolism inhibition

Gabriela Galicia-Vázquez  1   2   3 , Sarah Smith  1   2 , Raquel Aloyz  4   5   6   7
Affiliations

Del11q-positive CLL lymphocytes exhibit altered glutamine metabolism and differential response to GLS1 and glucose metabolism inhibition

Gabriela Galicia-Vázquez et al. Blood Cancer J. .
No abstract available

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1. Del11q CLL lymphocytes display glutamine metabolic alterations.
a, g Survival fraction (relative to non-treated control (NT)) of CLL lymphocytes treated with metabolic inhibitors for 48 h. a n = 23, g n = 19. b Ammonia uptake after 24 h compound 968 treatment (n = 14). c GS (n = 13) and d GDH (n = 13). Western blot of samples treated with compound 968 for 24 h. Representative images (upper panel) and quantification (lower panel) are shown. e Relative ROS values after 24 h treatment (n = 19, n (968 + NAC) = 8). f Population median value of total glutathione after 24 h of compound 968 treatment (n = 12). NS, not significant, *p < 0.05, **p < 0.001
Fig. 2
Fig. 2. Effect of glucose metabolic inhibitors and ibrutinib on CLL metabolism.
a, c, e, f Survival fraction (relative to non-treated control (NT)) of CLL lymphocytes treated with metabolic inhibitors for 48 h. b n = 21, c n = 12, e n = 19, f n = 23. b Glucose uptake after 24 h compound treatment (n = 15). d Relative ROS median values of CLL cells after 24 h of ibrutinib and/or NAC treatment (n = 20). *p < 0.05, **p < 0.001. g Model for basal wild-type and del11q CLL cell metabolism. The proposed metabolic flux in CLL lymphocytes is indicated with brown (wild-type) and pink (del11q) arrows. Del11q CLL lymphocytes promote glutamine synthesis, while decreasing GDH reaction. Glutamate production might be maintained via amino-acid catabolism through transaminase reactions, while glycolysis could provide the necessary metabolites to feed the TCA, PPP, and one-carbon metabolism. Wild-type CLL lymphocytes have a significant flux of glucose-derived carbons through PPP, while their amino-acid metabolism tends to generate ammonia
See this image and copyright information in PMC

References

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