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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/154867
A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression
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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.
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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. A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression. _Nature Communications_. 2018. Vol. 9, núm. 1787. [consulta: 15 de gener de 2026]. ISSN: 2041-1723. [Disponible a: https://hdl.handle.net/2445/154867]