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

Autor: Cristina Tecchio, Elda Mimiola, Aldo Scarpa, Giorgio Malpeli, Omar Perbellini, Martina Tinelli, Ornella Lovato, Maria Teresa Scupoli, Giovanni Pizzolo, Marco A. Cassatella, Fiorenza Aprili, Elisa Zoratti, Alberto Zamò, Chiara Cavallini, Anna Bertolaso
Rok vydání: 2015
Předmět:
Adult
Tumor Necrosis Factor Ligand Superfamily Member 15
Chronic lymphocytic leukemia
Blotting
Western
B-cell receptor
Fluorescent Antibody Technique
Apoptosis
cytokine receptors
Biology
Real-Time Polymerase Chain Reaction
Flow cytometry
immune system diseases
hemic and lymphatic diseases
Biomarkers
Tumor
Tumor Cells
Cultured
medicine
Humans
RNA
Messenger
Receptor
Receptors
Tumor Necrosis Factor
Member 25
Aged
Cell Proliferation
Neoplasm Staging
Aged
80 and over
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
Cell growth
leukemia
chronic lymphocytic leukemia
cytokines
microenvironment
Middle Aged
Flow Cytometry
Prognosis
Acquired immune system
medicine.disease
Leukemia
Lymphocytic
Chronic
B-Cell
Leukemia
Oncology
Case-Control Studies
Immunology
Female
Death receptor 3
Research Paper
Follow-Up Studies
Zdroj: Oncotarget
ISSN: 1949-2553
Popis: 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.
Databáze: OpenAIRE
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