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Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine

The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino ac...

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Autores principales: Bollino, Dominique, Claiborne, J. Preston, Hameed, Kanwal, Ma, Xinrong, Tighe, Kayla M., Carter-Cooper, Brandon, Lapidus, Rena G., Strovel, Erin T., Emadi, Ashkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790920/
https://www.ncbi.nlm.nih.gov/pubmed/36578934
http://dx.doi.org/10.3389/fonc.2022.1035537
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author Bollino, Dominique
Claiborne, J. Preston
Hameed, Kanwal
Ma, Xinrong
Tighe, Kayla M.
Carter-Cooper, Brandon
Lapidus, Rena G.
Strovel, Erin T.
Emadi, Ashkan
author_facet Bollino, Dominique
Claiborne, J. Preston
Hameed, Kanwal
Ma, Xinrong
Tighe, Kayla M.
Carter-Cooper, Brandon
Lapidus, Rena G.
Strovel, Erin T.
Emadi, Ashkan
author_sort Bollino, Dominique
collection PubMed
description The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino acid panel measurements in healthy immunodeficient/immunocompetent mice as well as in preclinical mouse models of acute myeloid leukemia (AML) and pancreatic ductal adenocarcinoma (PDAC) using long-acting crisantaspase, and in an AML clinical study (NCT02283190) using short-acting crisantaspase. In addition to the expected decrease of plasma glutamine and asparagine, we observed a significant increase in plasma serine and glycine post-crisantaspase. In PDAC tumors, crisantaspase treatment significantly increased expression of serine biosynthesis enzymes. We then systematically reviewed clinical studies using asparaginase products to determine the extent of plasma amino acid reporting and found that only plasma levels of glutamine/glutamate and asparagine/aspartate were reported, without measuring other amino acid changes post-asparaginase. To the best of our knowledge, we are the first to report comprehensive plasma amino acid changes in mice and humans treated with asparaginase. As dysregulated serine metabolism has been implicated in tumor development, our findings offer insights into how leukemia/cancer cells may potentially overcome glutamine/asparagine restriction, which can be used to design future synergistic therapeutic approaches.
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spelling pubmed-97909202022-12-27 Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine Bollino, Dominique Claiborne, J. Preston Hameed, Kanwal Ma, Xinrong Tighe, Kayla M. Carter-Cooper, Brandon Lapidus, Rena G. Strovel, Erin T. Emadi, Ashkan Front Oncol Oncology The impact of asparaginases on plasma asparagine and glutamine is well established. However, the effect of asparaginases, particularly those derived from Erwinia chrysanthemi (also called crisantaspase), on circulating levels of other amino acids is unknown. We examined comprehensive plasma amino acid panel measurements in healthy immunodeficient/immunocompetent mice as well as in preclinical mouse models of acute myeloid leukemia (AML) and pancreatic ductal adenocarcinoma (PDAC) using long-acting crisantaspase, and in an AML clinical study (NCT02283190) using short-acting crisantaspase. In addition to the expected decrease of plasma glutamine and asparagine, we observed a significant increase in plasma serine and glycine post-crisantaspase. In PDAC tumors, crisantaspase treatment significantly increased expression of serine biosynthesis enzymes. We then systematically reviewed clinical studies using asparaginase products to determine the extent of plasma amino acid reporting and found that only plasma levels of glutamine/glutamate and asparagine/aspartate were reported, without measuring other amino acid changes post-asparaginase. To the best of our knowledge, we are the first to report comprehensive plasma amino acid changes in mice and humans treated with asparaginase. As dysregulated serine metabolism has been implicated in tumor development, our findings offer insights into how leukemia/cancer cells may potentially overcome glutamine/asparagine restriction, which can be used to design future synergistic therapeutic approaches. Frontiers Media S.A. 2022-12-12 /pmc/articles/PMC9790920/ /pubmed/36578934 http://dx.doi.org/10.3389/fonc.2022.1035537 Text en Copyright © 2022 Bollino, Claiborne, Hameed, Ma, Tighe, Carter-Cooper, Lapidus, Strovel and Emadi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Bollino, Dominique
Claiborne, J. Preston
Hameed, Kanwal
Ma, Xinrong
Tighe, Kayla M.
Carter-Cooper, Brandon
Lapidus, Rena G.
Strovel, Erin T.
Emadi, Ashkan
Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title_full Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title_fullStr Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title_full_unstemmed Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title_short Erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
title_sort erwinia asparaginase (crisantaspase) increases plasma levels of serine and glycine
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9790920/
https://www.ncbi.nlm.nih.gov/pubmed/36578934
http://dx.doi.org/10.3389/fonc.2022.1035537
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