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Elastin MIcrofibriL INterfacer1 (EMILIN‐1) is an alternative prosurvival VLA‐4 ligand in chronic lymphocytic leukemia.

Authors :
Tissino, Erika
Pivetta, Eliana
Capuano, Alessandra
Capasso, Guido
Bomben, Riccardo
Caldana, Chiara
Rossi, Francesca Maria
Pozzo, Federico
Benedetti, Dania
Boldorini, Renzo
Gaidano, Gianluca
Rossi, Davide
Zamò, Alberto
Hartmann, Tanja Nicole
Doliana, Roberto
Colombatti, Alfonso
Gattei, Valter
Spessotto, Paola
Zucchetto, Antonella
Source :
Hematological Oncology; Apr2022, Vol. 40 Issue 2, p181-190, 10p
Publication Year :
2022

Abstract

CD49d, the α4 chain of the VLA‐4 integrin, is a negative prognosticator in chronic lymphocytic leukemia (CLL) with a key role in CLL cell‐microenvironment interactions mainly occurring via its ligands VCAM‐1 and fibronectin. In the present study, we focused on EMILIN‐1 (Elastin‐MIcrofibriL‐INterfacer‐1), an alternative VLA‐4 ligand whose role has been so far reported only in non‐hematological settings, by investigating: i) the distribution of EMILIN‐1 in CLL‐involved tissues; ii) the capability of EMILIN‐1 to operate, via its globular C1q (gC1q) domain, as additional adhesion ligand in CLL; iii) the functional meaning of EMILIN‐1 gC1q/VLA‐4 interactions in CLL. EMILIN‐1 is widely present in the CLL‐involved areas of bone marrow biopsies (BMBs) without difference between CD49d negative and positive cases, displaying at least three different expression patterns: "fibrillar", "dot‐like" and "mixed". The lack in CLL‐BMB of neutrophil elastase, whose proteolytic activity degrades EMILIN‐1 and impairs EMILIN‐1 function, suggests full functional EMILIN‐1 in CLL independently of its expression pattern. Functionally, EMILIN‐1 gC1q domain promotes adhesion of CLL cells through specific interaction with VLA‐4, and releases pro‐survival signals for CLL cells, as demonstrated by enhanced ERK and AKT phosphorylation and impairment of in‐vitro‐induced apoptosis. EMILIN‐1/VLA‐4 interaction can efficiently contribute to the maintenance of the neoplastic clone in CLL. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02780232
Volume :
40
Issue :
2
Database :
Complementary Index
Journal :
Hematological Oncology
Publication Type :
Academic Journal
Accession number :
156131966
Full Text :
https://doi.org/10.1002/hon.2947