A retinoic acid-dependent stroma-leukemia crosstalk promotes chronic lymphocytic leukemia progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Diego Farinello, Monika Wozińska, Elisa Lenti, Luca Genovese, Silvia Bianchessi, Edoardo Migliori, Nicolò Sacchetti, Alessia di Lillo, Maria Teresa Sabrina Bertilaccio, Claudia de Lalla, Roberta Valsecchi, Sabrina Bascones Gleave, David Lligé, Cristina Scielzo, Laura Mauri, Maria Grazia Ciampa, Lydia Scarfò, Rosa Bernardi, Dejan Lazarevic, Blanca Gonzalez-Farre, Lucia Bongiovanni, Elias Campo, Andrea Cerutti, Maurilio Ponzoni, Linda Pattini, Federico Caligaris-Cappio, Paolo Ghia, Andrea Brendolan

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. More... »

PAGES

1787

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-04150-7

DOI

http://dx.doi.org/10.1038/s41467-018-04150-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1103702809

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29725010


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443 schema:name Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), 08003, Barcelona, Spain
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445 https://www.grid.ac/institutes/grid.240145.6 schema:alternateName The University of Texas MD Anderson Cancer Center
446 schema:name Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, 77054 TX, Houston, USA
447 Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, 20132, Milan, Italy
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450 schema:name Associazione Italiana per la Ricerca sul Cancro, Via San Vito 7, 20123, Milano, Italy
451 Division of Experimental Oncology, IRCCS, San Raffaele Scientific Institute, 20132, Milan, Italy
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453 https://www.grid.ac/institutes/grid.4643.5 schema:alternateName Polytechnic University of Milan
454 schema:name Department of Electronics, Information and Bioengineering, Politecnico di Milano, 20133, Milan, Italy
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456 https://www.grid.ac/institutes/grid.4708.b schema:alternateName University of Milan
457 schema:name Department of Medical Biotechnology and Translational Medicine, University of Milan, 20090, Milano, Italy
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459 https://www.grid.ac/institutes/grid.5841.8 schema:alternateName University of Barcelona
460 schema:name Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic and University of Barcelona, Calle Roselló 149-153, 08036, Barcelona, Spain
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