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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
Notes:	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.
Subject(s):	-Retinoides -Leucèmia limfocítica crònica -Citoquines -Retinoids -Chronic lymphocytic leukemia -Cytokines
Rights:	cc-by (c) Farinello, D. et al., 2018 http://creativecommons.org/licenses/by/3.0/es
Document type:	Article Article - Published version
Published by:	Nature Publishing Group
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