Farinello, DiegoWozińska, MonikaLenti, ElisaGenovese, LucaBianchessi, SilviaMigliori, EdoardoSacchetti, Nicolòdi Lillo, AlessiaBertilaccio, Maria Teresa Sabrinade Lalla, ClaudiaValsecchi, RobertaGleave, Sabrina BasconesLligé, DavidScielzo, CristinaMauri, LauraCiampa, Maria GraziaScarfò, LydiaBernardi, RosaLazarevic, DejanGonzález Farré, BlancaBongiovanni, LuciaCampo Güerri, EliasCerutti, AndreaPonzoni, MaurilioPattini, LindaCaligaris-Cappio, FedericoGhia, PaoloBrendolan, Andrea2020-04-022020-04-022018-05-032041-1723https://hdl.handle.net/2445/154867In 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.12 p.application/pdfengcc-by (c) Farinello, D. et al., 2018http://creativecommons.org/licenses/by/3.0/esRetinoidesLeucèmia limfocítica crònicaCitoquinesRetinoidsChronic lymphocytic leukemiaCytokinesinfo:eu-repo/semantics/article6803922020-04-02info:eu-repo/semantics/openAccess29725010