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Title: | A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression |
Author: | Farinello, Diego Wozińska, Monika Lenti, Elisa Genovese, Luca Bianchessi, Silvia Migliori, Edoardo Sacchetti, Nicolò di Lillo, Alessia Bertilaccio, Maria Teresa Sabrina de Lalla, Claudia Valsecchi, Roberta Gleave, Sabrina Bascones Lligé, David Scielzo, Cristina Mauri, Laura Ciampa, Maria Grazia Scarfò, Lydia Bernardi, Rosa Lazarevic, Dejan González Farré, Blanca Bongiovanni, Lucia Campo Güerri, Elias Cerutti, Andrea Ponzoni, Maurilio Pattini, Linda Caligaris-Cappio, Federico Ghia, Paolo Brendolan, Andrea |
Keywords: | Retinoides Leucèmia limfocítica crònica Citoquines Retinoids Chronic lymphocytic leukemia Cytokines |
Issue Date: | 3-May-2018 |
Publisher: | Nature Publishing Group |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41467-018-04150-7 |
It is part of: | Nature Communications, 2018, vol. 9, p. 1787 |
URI: | http://hdl.handle.net/2445/154867 |
Related resource: | https://doi.org/10.1038/s41467-018-04150-7 |
ISSN: | 2041-1723 |
Appears in Collections: | Articles publicats en revistes (Fonaments Clínics) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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