A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression

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• dc.contributor.author Farinello, Diego
• dc.contributor.author Bascones Gleave, Sabrina, 1985-
• dc.contributor.author Lligé, David
• dc.contributor.author Brendolan, Andrea
• dc.date.accessioned 2019-06-13T06:24:24Z
• dc.date.available 2019-06-13T06:24:24Z
• dc.date.issued 2018
• dc.description.abstract In chronic lymphocytic leukemia (CLL), the non-hematopoietic stromal microenvironment plays a critical role in promoting tumor cell recruitment, activation, survival, and expansion. However, the nature of the stromal cells and molecular pathways involved remain largely unknown. Here, we demonstrate that leukemic B lymphocytes induce the activation of retinoid acid synthesis and signaling in the microenvironment. Inhibition of RA-signaling in stromal cells causes deregulation of genes associated with adhesion, tissue organization and chemokine secretion including the B-cell chemokine CXCL13. Notably, reducing retinoic acid precursors from the diet or inhibiting RA-signaling through retinoid-antagonist therapy prolong survival by preventing dissemination of leukemia cells into lymphoid tissues. Furthermore, mouse and human leukemia cells could be distinguished from normal B-cells by their increased expression of Rarγ2 and RXRα, respectively. These findings establish a role for retinoids in murine CLL pathogenesis, and provide new therapeutic strategies to target the microenvironment and to control disease progression.
• dc.format.mimetype application/pdf
• dc.identifier.citation Farinello D, Wozińska M, Lenti E, Genovese L, Bianchessi S, Migliori E. et al. A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression. Nat Commun. 2018 May 3;9(1):1787. DOI: 10.1038/s41467-018-04150-7
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-04150-7
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/41748
• dc.language.iso eng
• dc.publisher Nature Research
• dc.rights Copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Leucèmia limfocítica crònica
• dc.subject.other Limfomes
• dc.title A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion