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Type: Artigo de periódico
Title: Lymphotoxin-beta Receptor In Microenvironmental Cells Promotes The Development Of T-cell Acute Lymphoblastic Leukaemia With Cortical/mature Immunophenotype
Author: Fernandes
Monica T.; Ghezzo
Marinella N.; Silveira
Andre B.; Kalathur
Ravi K.; Povoa
Vanda; Ribeiro
Ana R.; Brandalise
Silvia R.; Dejardin
Emmanuel; Alves
Nuno L.; Ghysdael
Jacques; Barata
Joao T.; Yunes
Jose Andres; dos Santos
Nuno R.
Abstract: Lymphotoxin-mediated activation of the lymphotoxin-beta receptor (LT beta R; LTBR) has been implicated in cancer, but its role in T-cell acute lymphoblastic leukaemia (T-ALL) has remained elusive. Here we show that the genes encoding lymphotoxin (LT)-alpha and LIP (LTA, LTB) arc expressed in T-ALL patient samples, mostly of the TAL/LMO molecular subtype, and in the TEL-JAK2 transgenic mouse model of cortical/mature T-ALL (Lta, Ltb). In these mice, expression of Lta and Ltb is elevated in early stage TALL. Surface LT 132 protein is expressed in primary mouse T-ALL cells, but only in the absence of microenvironmental LT beta R interaction. Indeed, surface LT expression is suppressed in leukaemic cells contacting Ltbr-expressing but not Ltbr-deficient stromal cells, both in vitro and in vivo, thus indicating that dynamic surface LT expression in leukaemic cells depends on interaction with its receptor. Supporting the notion that LT signalling plays a role in T-ALL, inactivation of Ltbr results in a significant delay in TEL-JAK2-induced leukaemia onset. Moreover, young asymptomatic TEL-JAK2;Ltbr(-/-) mice present markedly less leukaemic thymocytcs than age-matched TEL-JAK2;Ltbr(+/+) mice and interference with LT beta R function at this early stage delayed I-ALL development. We conclude that LT expression by T-ALL cells activates LT beta R signalling in thymic stromal cells, thus promoting leukaemogenesis.
Subject: Nf-kappa-b
Thymic Stromal Cells
Country: HOBOKEN
Citation: Lymphotoxin-beta Receptor In Microenvironmental Cells Promotes The Development Of T-cell Acute Lymphoblastic Leukaemia With Cortical/mature Immunophenotype. Wiley-blackwell, v. 171, p. 736-751 DEC-2015.
Rights: fechado
Identifier DOI: 10.1111/bjh.13760
Date Issue: 2015
Appears in Collections:Unicamp - Artigos e Outros Documentos

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