Oncotarget

Research Papers:

Cross-talk between chronic lymphocytic leukemia (CLL) tumor B cells and mesenchymal stromal cells (MSCs): implications for neoplastic cell survival

Valentina Trimarco _, Elisa Ave, Monica Facco, Giorgia Chiodin, Federica Frezzato, Veronica Martini, Cristina Gattazzo, Federica Lessi, Carlo Alberto Giorgi, Andrea Visentin, Monica Castelli, Filippo Severin, Renato Zambello, Francesco Piazza, Gianpietro Semenzato and Livio Trentin

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Oncotarget. 2015; 6:42130-42149. https://doi.org/10.18632/oncotarget.6239

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Abstract

Valentina Trimarco1,2,*, Elisa Ave1,2,*, Monica Facco1,2, Giorgia Chiodin1,2, Federica Frezzato1,2, Veronica Martini1,2, Cristina Gattazzo1,2, Federica Lessi1, Carlo Alberto Giorgi1, Andrea Visentin1, Monica Castelli1, Filippo Severin1,2, Renato Zambello1,2, Francesco Piazza1,2, Gianpietro Semenzato1,2 and Livio Trentin1,2

1 Padua University School of Medicine, Department of Medicine, Hematology and Clinical Immunology Branch, Padua, Italy

2 Venetian Institute of Molecular Medicine (VIMM), Padua, Italy

* These authors have contributed equally to this manuscript

Correspondence to:

Livio Trentin, email:

Gianpietro Semenzato, email:

Keywords: chronic lymphocytic leukemia, mesenchymal stromal cells, kinase inhibitors

Received: April 29, 2015 Accepted: October 05, 2015 Published: October 26, 2015

Abstract

Leukemic cells from Chronic Lymphocytic Leukemia (CLL) patients interact with stromal cells of the surrounding microenvironment. Mesenchymal Stromal Cells (MSCs) represent the main population in CLL marrow stroma, which may play a key role for disease support and progression. In this study we evaluated whether MSCs influence in vitro CLL cell survival. MSCs were isolated from the bone marrow of 46 CLL patients and were characterized by flow cytometry analysis. Following co-culture of MSCs and leukemic B cells, we demonstrated that MSCs were able to improve leukemic B cell viability, this latter being differently dependent from the signals coming from MSCs. In addition, we found that the co-culture of MSCs with leukemic B cells induced an increased production of IL-8, CCL4, CCL11, and CXCL10 chemokines.

As far as drug resistance is concerned, MSCs counteract the cytotoxic effect of Fludarabine/Cyclophosphamide administration in vivo, whereas they do not protect CLL cells from the apoptosis induced by the kinase inhibitors Bafetinib and Ibrutinib. The evidence that leukemic clones are conditioned by environmental stimuli suggest new putative targets for therapy in CLL patients.


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