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CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia
Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a coho...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for Cancer Research
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472106/ https://www.ncbi.nlm.nih.gov/pubmed/37327406 http://dx.doi.org/10.1158/0008-5472.CAN-22-3682 |
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author | Farge, Thomas Nakhle, Jean Lagarde, Damien Cognet, Guillaume Polley, Nathaniel Castellano, Rémy Nicolau, Marie-Laure Bosc, Claudie Sabatier, Marie Sahal, Ambrine Saland, Estelle Jeanson, Yannick Guiraud, Nathan Boet, Emeline Bergoglio, Camille Gotanègre, Mathilde Mouchel, Pierre-Luc Stuani, Lucille Larrue, Clément Sallese, Marie De Mas, Véronique Moro, Cedric Dray, Cédric Collette, Yves Raymond-Letron, Isabelle Ader, Isabelle Récher, Christian Sarry, Jean-Emmanuel Cabon, Florence Vergez, François Carrière, Audrey |
author_facet | Farge, Thomas Nakhle, Jean Lagarde, Damien Cognet, Guillaume Polley, Nathaniel Castellano, Rémy Nicolau, Marie-Laure Bosc, Claudie Sabatier, Marie Sahal, Ambrine Saland, Estelle Jeanson, Yannick Guiraud, Nathan Boet, Emeline Bergoglio, Camille Gotanègre, Mathilde Mouchel, Pierre-Luc Stuani, Lucille Larrue, Clément Sallese, Marie De Mas, Véronique Moro, Cedric Dray, Cédric Collette, Yves Raymond-Letron, Isabelle Ader, Isabelle Récher, Christian Sarry, Jean-Emmanuel Cabon, Florence Vergez, François Carrière, Audrey |
author_sort | Farge, Thomas |
collection | PubMed |
description | Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients. SIGNIFICANCE: CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment. |
format | Online Article Text |
id | pubmed-10472106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for Cancer Research |
record_format | MEDLINE/PubMed |
spelling | pubmed-104721062023-09-02 CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia Farge, Thomas Nakhle, Jean Lagarde, Damien Cognet, Guillaume Polley, Nathaniel Castellano, Rémy Nicolau, Marie-Laure Bosc, Claudie Sabatier, Marie Sahal, Ambrine Saland, Estelle Jeanson, Yannick Guiraud, Nathan Boet, Emeline Bergoglio, Camille Gotanègre, Mathilde Mouchel, Pierre-Luc Stuani, Lucille Larrue, Clément Sallese, Marie De Mas, Véronique Moro, Cedric Dray, Cédric Collette, Yves Raymond-Letron, Isabelle Ader, Isabelle Récher, Christian Sarry, Jean-Emmanuel Cabon, Florence Vergez, François Carrière, Audrey Cancer Res Cancer Biology Identifying mechanisms underlying relapse is a major clinical issue for effective cancer treatment. The emerging understanding of the importance of metastasis in hematologic malignancies suggests that it could also play a role in drug resistance and relapse in acute myeloid leukemia (AML). In a cohort of 1,273 AML patients, we uncovered that the multifunctional scavenger receptor CD36 was positively associated with extramedullary dissemination of leukemic blasts, increased risk of relapse after intensive chemotherapy, and reduced event-free and overall survival. CD36 was dispensable for lipid uptake but fostered blast migration through its binding with thrombospondin-1. CD36-expressing blasts, which were largely enriched after chemotherapy, exhibited a senescent-like phenotype while maintaining their migratory ability. In xenograft mouse models, CD36 inhibition reduced metastasis of blasts and prolonged survival of chemotherapy-treated mice. These results pave the way for the development of CD36 as an independent marker of poor prognosis in AML patients and a promising actionable target to improve the outcome of patients. SIGNIFICANCE: CD36 promotes blast migration and extramedullary disease in acute myeloid leukemia and represents a critical target that can be exploited for clinical prognosis and patient treatment. American Association for Cancer Research 2023-09-01 2023-06-16 /pmc/articles/PMC10472106/ /pubmed/37327406 http://dx.doi.org/10.1158/0008-5472.CAN-22-3682 Text en ©2023 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
spellingShingle | Cancer Biology Farge, Thomas Nakhle, Jean Lagarde, Damien Cognet, Guillaume Polley, Nathaniel Castellano, Rémy Nicolau, Marie-Laure Bosc, Claudie Sabatier, Marie Sahal, Ambrine Saland, Estelle Jeanson, Yannick Guiraud, Nathan Boet, Emeline Bergoglio, Camille Gotanègre, Mathilde Mouchel, Pierre-Luc Stuani, Lucille Larrue, Clément Sallese, Marie De Mas, Véronique Moro, Cedric Dray, Cédric Collette, Yves Raymond-Letron, Isabelle Ader, Isabelle Récher, Christian Sarry, Jean-Emmanuel Cabon, Florence Vergez, François Carrière, Audrey CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title | CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title_full | CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title_fullStr | CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title_full_unstemmed | CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title_short | CD36 Drives Metastasis and Relapse in Acute Myeloid Leukemia |
title_sort | cd36 drives metastasis and relapse in acute myeloid leukemia |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472106/ https://www.ncbi.nlm.nih.gov/pubmed/37327406 http://dx.doi.org/10.1158/0008-5472.CAN-22-3682 |
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