Oncotarget

Research Papers:

Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia

Chiara Cavallini _, Ornella Lovato, Anna Bertolaso, Elisa Zoratti, Giorgio Malpeli, Elda Mimiola, Martina Tinelli, Fiorenza Aprili, Cristina Tecchio, Omar Perbellini, Aldo Scarpa, Alberto Zamò, Marco Antonio Cassatella, Giovanni Pizzolo and Maria Teresa Scupoli

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Oncotarget. 2015; 6:32061-32074. https://doi.org/10.18632/oncotarget.5201

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Abstract

Chiara Cavallini1, Ornella Lovato1, Anna Bertolaso2, Elisa Zoratti1,3, Giorgio Malpeli2,3, Elda Mimiola4, Martina Tinelli4, Fiorenza Aprili5, Cristina Tecchio4, Omar Perbellini4, Aldo Scarpa2,3, Alberto Zamò2, Marco Antonio Cassatella6, Giovanni Pizzolo4, Maria Teresa Scupoli1,3,4

1Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy

2Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona, Italy

3Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy

4Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

5Department of Pathology and Diagnostics, Laboratory of Cytogenetics, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

6Department of Pathology and Diagnostics, Section of General Pathology, University of Verona, Verona, Italy

Correspondence to:

Maria Teresa Scupoli, e-mail: mariateresa.scupoli@univr.it

Keywords: leukemia, microenvironment, chronic lymphocytic leukemia, cytokines, cytokine receptors

Received: July 31, 2015     Accepted: September 04, 2015     Published: September 15, 2015

ABSTRACT

TNF-like ligand 1A (TL1A) and its unique receptor death receptor 3 (DR3) acts as broad T-cell costimulator involved in regulatory mechanisms of adaptive immune response under physiological and pathological settings. Moreover, we have recently shown that TL1A negatively regulates B-cell proliferation. Despite increasing interest on the TL1A/DR3-axis functions, very little is known on its expression and role in leukemia. In this study, we investigated the expression and function of TL1A/DR3 axis in chronic lymphocytic leukemia (CLL). DR3 was differentially expressed in activated CLL cells and predominantly detected in patients with early clinical stage disease. Soluble TL1A has been revealed in the sera of CLL patients where higher TL1A levels were associated with early stage disease. T cells, monocytes and leukemic B cells have been identified as major sources of TL1A in CLL. The relevance of these findings has been sustained by functional data showing that exogenous TL1A reduces CLL proliferation induced by stimulation of the B cell receptor. Overall, these data document the expression of the TL1A/DR3 axis in early-stage CLL. They also identify a novel function for TL1A as a negative regulator of leukemic cell proliferation that may influence the CLL physiopathology and clinical outcome at an early-stage disease.


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