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|Titolo:||DEATH RECEPTOR 3 EXPRESSION AND SERUM LEVEL OF SOLUBLE TL1A CORRELATE WITH INDOLENT, EARLY STAGE B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA|
|Autori interni:||CAVALLINI, Chiara|
|Data di pubblicazione:||2014|
|Abstract:||Introduction. B-cell chronic lymphocytic leukemia (B-CLL) accounts for approximately 30% of leukemia diagnosed in the Western coun- tries and shows an increasing incidence with the age of the popula- tion. Analysis of survival times has led to the establishment of stag- ing systems according to various prognostic markers, including Rai stage, IGHV mutational status, expression of CD38 and Zap70. Clin- ically, B-CLL is a heterogeneous disease with variable presentation and evolution. Two major subtypes can be distinguished, indolent and aggressive, which require different treatment strategies. Howev- er, prediction of the clinical course of individual patients with the same stage and risk group remains variable. Receptors of the TNFR superfamily play a fundamental role in promoting the growth of B-cell chronic lymphocytic leukemia. Death receptor (DR) 3 is a TNFR- superfamily member expressed in lymphocyte-enriched tissues. DR3 and its ligand, TNF-like ligand 1A (TL1A), are implicated in regulato- ry mechanisms of adaptive immune response under physiological and pathological settings. Recently, we have demonstrated that DR3 is expressed on the surface of B cell receptor (BCR)-stimulated B cells and interaction of DR3 with TL1A reduces proliferation of suboptimally activated healthy B cells in vitro, without affecting cell survival. These findings prompted us to examine the expression of DR3 and TL1A in B-CLL and their possible role as risk factors for disease progression. Methods. DR3 surface expression of 37 B-CLL samples was measured by flow cytometry at baseline and following stimulation with F(ab’)2 anti-human IgM conjugated to latex microspheres. TL1A serum lev- els of 26 B-CLL samples were measured by ELISA. Correlation analy- sis with clinical and biological parameters were performed using GraphPad Prism software. Results. Here, our preliminary results show that DR3 is expressed on the surface of activated CLL B cells and TL1A is present in the serum of B-CLL patients. Moreover, we show that BCR-induced DR3 expression is more frequently detected in sam- ples with indolent, early-stage disease (Rai 0). The relevance of these findings has been confirmed by serum TL1A measurement showing that higher serum levels of TL1A are more frequently detected in B- CLL patients with favorable prognostic parameters (i.e. absence of CD38 expression) and early-stage disease. Conclusions. Taken togeth- er, these findings suggest that in B-CLL the TL1A/DR3 modulatory function on cell metabolism, in the presence of antigen stimulation, is a feature of indolent, early-stage disease. Thus, we can assume that these factors could be useful in monitoring disease activity and may be of prognostic relevance in B-CLL.|
|Appare nelle tipologie:||04.01 Contributo in atti di convegno|
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