| Literature DB >> 25398834 |
Stefania Fiorcari1, Silvia Martinelli1, Jenny Bulgarelli1, Valentina Audrito2, Patrizia Zucchini1, Elisabetta Colaci1, Leonardo Potenza1, Franco Narni1, Mario Luppi1, Silvia Deaglio2, Roberto Marasca3, Rossana Maffei1.
Abstract
Lenalidomide is an immunomodulatory agent clinically active in chronic lymphocytic leukemia patients. The specific mechanism of action is still undefined, but includes modulation of the microenvironment. In chronic lymphocytic leukemia patients, nurse-like cells differentiate from CD14(+) mononuclear cells and protect chronic lymphocytic leukemia cells from apoptosis. Nurse-like cells resemble M2 macrophages with potent immunosuppressive functions. Here, we examined the effect of lenalidomide on the monocyte/macrophage population in chronic lymphocytic leukemia patients. We found that lenalidomide induces high actin polymerization on CD14(+) monocytes through activation of small GTPases, RhoA, Rac1 and Rap1 that correlated with increased adhesion and impaired monocyte migration in response to CCL2, CCL3 and CXCL12. We observed that lenalidomide increases the number of nurse-like cells that lost the ability to nurture chronic lymphocytic leukemia cells, acquired properties of phagocytosis and promoted T-cell proliferation. Gene expression signature, induced by lenalidomide in nurse-like cells, indicated a reduction of pivotal pro-survival signals for chronic lymphocytic leukemia, such as CCL2, IGF1, CXCL12, HGF1, and supported a modulation towards M1 phenotype with high IL2 and low IL10, IL8 and CD163. Our data provide new insights into the mechanism of action of lenalidomide that mediates a pro-inflammatory switch of nurse-like cells affecting the protective microenvironment generated by chronic lymphocytic leukemia into tissues. Copyright© Ferrata Storti Foundation.Entities:
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Year: 2014 PMID： 25398834 PMCID： PMC4803140 DOI： 10.3324/haematol.2014.113217
Source DB: PubMed Journal: Haematologica ISSN： 0390-6078 Impact factor: 9.941