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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Farinello D,Wozińska M,Lenti E,Genovese L,Bianchessi S,Migliori E,Sacchetti N,di Lillo A,Bertilaccio MTS,de Lalla C,Valsecchi R,Gleave SB,Lligé D,Scielzo C,Mauri L,Ciampa MG,Scarfò L,Bernardi R,Lazarevic D,Gonzalez-doi
10.1038/s41467-018-04150-7subject
Has Abstractpub_date
2018-05-03 00:00:00pages
1787issue
1issn
2041-1723pii
10.1038/s41467-018-04150-7journal_volume
9pub_type
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