Metabolic signature and response to glutamine deprivation are independent of p53 status in B cell malignancies.

Autor:	Montironi C; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands., Chen Z; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands., Derks IAM; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands., Cretenet G; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands., Krap EA; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands., Eldering E; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands., Simon-Molas H; Amsterdam UMC Location University of Amsterdam, Department of Experimental Immunology, Amsterdam, the Netherlands.; Amsterdam Institute for Infection and Immunity, Cancer Immunology, Amsterdam, the Netherlands.; Cancer Center Amsterdam, Cancer Immunology, Amsterdam, the Netherlands.; Amsterdam UMC Location University of Amsterdam, Department of Hematology, Amsterdam, the Netherlands.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Mar 28; Vol. 27 (5), pp. 109640. Date of Electronic Publication: 2024 Mar 28 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.109640
Abstrakt:	The tumor suppressor p53 has been described to control various aspects of metabolic reprogramming in solid tumors, but in B cell malignancies that role is as yet unknown. We generated pairs of p53 functional and knockout (KO) clones from distinct B cell malignancies (acute lymphoblastic leukemia, chronic lymphocytic leukemia, diffuse large B cell lymphoma, and multiple myeloma). Metabolomics and isotope tracing showed that p53 loss did not drive a common metabolic signature. Instead, cell lines segregated according to cell of origin. Next, we focused on glutamine as a crucial energy source in the B cell tumor microenvironment. In both TP53 wild-type and KO cells, glutamine deprivation induced cell death through the integrated stress response, via CHOP/ATF4. Lastly, combining BH3 mimetic drugs with glutamine starvation emerged as a possibility to target resistant clones. In conclusion, our analyses do not support a common metabolic signature of p53 deficiency in B cell malignancies and suggest therapeutic options for exploration based on glutamine dependency. Competing Interests: The authors declare no competing interests. (© 2024 The Authors.)
Databáze:	MEDLINE
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