title: Expression and function of the TL1A/DR3 axis in chronic lymphocytic leukemia.
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.
authors.affiliation: Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cavallini
authors.affiliation: Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Lovato
authors.affiliation: Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bertolaso
authors.affiliation: Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.|Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Zoratti
authors.affiliation: Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona, Italy.|Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Malpeli
authors.affiliation: Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Elda
authors.initials: E
authors.lastname: Mimiola
authors.affiliation: Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Tinelli
authors.affiliation: Department of Pathology and Diagnostics, Laboratory of Cytogenetics, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Aprili
authors.affiliation: Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tecchio
authors.affiliation: Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.affiliation: Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona, Italy.|Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Department of Pathology and Diagnostics, Section of Pathological Anatomy, University of Verona, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamò
authors.affiliation: Department of Pathology and Diagnostics, Section of General Pathology, University of Verona, Verona, Italy.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Cassatella
authors.affiliation: Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.affiliation: Interdepartmental Laboratory of Medical Research (LURM), University of Verona, Verona, Italy.|Applied Research on Cancer-Network (ARC-NET), University of Verona, Verona, Italy.|Department of Medicine, Section of Hematology, University of Verona, Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Scupoli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D053219:Receptors, Tumor Necrosis Factor, Member 25 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15
keywords: chronic lymphocytic leukemia; cytokine receptors; cytokines; leukemia; microenvironment