| Added by | Nathalie Bonnefoy |
|---|---|
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | Extracellular ATP and CD39 activate cAMP-mediated mitochondrial stress response to promote cytarabine resistance in acute myeloid leukemia |
| Creator | Aroua et al. |
| Author | Nesrine Aroua |
| Author | Emeline Boet |
| Author | Margherita Ghisi |
| Author | Marie-Laure Nicolau-Travers |
| Author | Estelle Saland |
| Author | Ryan Gwilliam |
| Author | Fabienne de Toni |
| Author | Mohsen Hosseini |
| Author | Pierre-Luc Mouchel |
| Author | Thomas Farge |
| Author | Claudie Bosc |
| Author | Lucille Stuani |
| Author | Marie Sabatier |
| Author | Fetta Mazed |
| Author | Latifa Jarrou |
| Author | Sarah Gandarillas |
| Author | Massimiliano Bardotti |
| Author | Muriel Picard |
| Author | Charlotte Syrykh |
| Author | Camille Laurent |
| Author | Mathilde Gotanegre |
| Author | Nathalie Bonnefoy |
| Author | Floriant Bellvert |
| Author | Jean-Charles Portais |
| Author | Nathalie Nicot |
| Author | Francisco Azuaje |
| Author | Tony Kaoma |
| Author | Carine Joffre |
| Author | Jerome Tamburini |
| Author | Jean-Emmanuel Sarry |
| Abstract | Relapses driven by chemoresistant leukemic cell populations are the main cause of mortality for patients with acute myeloid leukemia (AML). Here, we show that the ectonucleotidase CD39 (ENTPD1) is upregulated in cytarabine (AraC)-resistant leukemic cells from both AML cell lines and patient samples in vivo and in vitro. CD39 cell surface expression and activity is increased in AML patients upon chemotherapy compared to diagnosis and enrichment in CD39-expressing blasts is a marker of adverse prognosis in the clinics. High CD39 activity promotes AraC resistance by enhancing mitochondrial activity and biogenesis through activation of a cAMP-mediated adaptive mitochondrial stress response. Finally, genetic and pharmacological inhibition of CD39 eATPase activity blocks the mitochondrial reprogramming triggered by AraC treatment and markedly enhances its cytotoxicity in AML cells in vitro and in vivo. Together, these results reveal CD39 as a new residual disease marker and a promising therapeutic target to improve chemotherapy response in AML. |
| Publication | Cancer Discovery |
| Date | Jul 08, 2020 |
| Journal Abbr | Cancer Discov |
| Language | eng |
| DOI | 10.1158/2159-8290.CD-19-1008 |
| ISSN | 2159-8290 |
| Library Catalog | PubMed |
| Extra | PMID: 32641297 |
| Tags | cancer, CD39, chemoresistance, original |
| Date Added | 2020/07/29 - 15:14:25 |
| Date Modified | 2020/07/29 - 15:29:43 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
