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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
Chronic lymphocytic leukemia
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.
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It is part of: Nature Communications, 2018, vol. 9, p. 1787
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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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