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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2023
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.
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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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