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Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL)
BL and DLBCL are subtypes of B-cell lymphomas that arise from germinal centre B lymphocytes. Differentiation between BL and DLBCL is critical and can be challenging, as these two types of cancer share the same morphological, immunophenotypic, and genetic characteristics. In this study, we have exami...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533740/ https://www.ncbi.nlm.nih.gov/pubmed/34685569 http://dx.doi.org/10.3390/cells10102589 |
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author | Eraslan, Zuhal Papatzikas, Grigorios Cazier, Jean-Baptiste Khanim, Farhat L. Günther, Ulrich L. |
author_facet | Eraslan, Zuhal Papatzikas, Grigorios Cazier, Jean-Baptiste Khanim, Farhat L. Günther, Ulrich L. |
author_sort | Eraslan, Zuhal |
collection | PubMed |
description | BL and DLBCL are subtypes of B-cell lymphomas that arise from germinal centre B lymphocytes. Differentiation between BL and DLBCL is critical and can be challenging, as these two types of cancer share the same morphological, immunophenotypic, and genetic characteristics. In this study, we have examined metabolism in BL and DLBCL lymphomas and found distinctive differences in serine metabolism. We show that BL cells consume significantly more extracellular asparagine than DLBCL cells. Using a tracer-based approach, we find that asparagine regulates the serine uptake and serine synthesis in BL and DLBCL cells. Calculation of Differentially Expressed Genes (DEGs) from RNAseq datasets of BL and DLBCL patients show that BL cancers express the genes involved in serine synthesis at a higher level than DLBCL. Remarkably, combined use of an inhibitor of serine biosynthesis pathway and an anticancer drug asparaginase increases the sensitivity of BL cells to extracellular asparagine deprivation without inducing a change in the sensitivity of DLBCL cells to asparaginase. In summary, our study unravels metabolic differences between BL and DLBCL with diagnostic potential which may also open new avenues for treatment. |
format | Online Article Text |
id | pubmed-8533740 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85337402021-10-23 Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) Eraslan, Zuhal Papatzikas, Grigorios Cazier, Jean-Baptiste Khanim, Farhat L. Günther, Ulrich L. Cells Article BL and DLBCL are subtypes of B-cell lymphomas that arise from germinal centre B lymphocytes. Differentiation between BL and DLBCL is critical and can be challenging, as these two types of cancer share the same morphological, immunophenotypic, and genetic characteristics. In this study, we have examined metabolism in BL and DLBCL lymphomas and found distinctive differences in serine metabolism. We show that BL cells consume significantly more extracellular asparagine than DLBCL cells. Using a tracer-based approach, we find that asparagine regulates the serine uptake and serine synthesis in BL and DLBCL cells. Calculation of Differentially Expressed Genes (DEGs) from RNAseq datasets of BL and DLBCL patients show that BL cancers express the genes involved in serine synthesis at a higher level than DLBCL. Remarkably, combined use of an inhibitor of serine biosynthesis pathway and an anticancer drug asparaginase increases the sensitivity of BL cells to extracellular asparagine deprivation without inducing a change in the sensitivity of DLBCL cells to asparaginase. In summary, our study unravels metabolic differences between BL and DLBCL with diagnostic potential which may also open new avenues for treatment. MDPI 2021-09-29 /pmc/articles/PMC8533740/ /pubmed/34685569 http://dx.doi.org/10.3390/cells10102589 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Eraslan, Zuhal Papatzikas, Grigorios Cazier, Jean-Baptiste Khanim, Farhat L. Günther, Ulrich L. Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title | Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title_full | Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title_fullStr | Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title_full_unstemmed | Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title_short | Targeting Asparagine and Serine Metabolism in Germinal Centre-Derived B Cells Non-Hodgkin Lymphomas (B-NHL) |
title_sort | targeting asparagine and serine metabolism in germinal centre-derived b cells non-hodgkin lymphomas (b-nhl) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533740/ https://www.ncbi.nlm.nih.gov/pubmed/34685569 http://dx.doi.org/10.3390/cells10102589 |
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