Lymphotoxin-beta Receptor In Microenvironmental Cells Promotes The Development Of T-cell Acute Lymphoblastic Leukaemia With Cortical/mature Immunophenotype

dc.creatorFernandes
dc.creatorMonica T.; Ghezzo
dc.creatorMarinella N.; Silveira
dc.creatorAndre B.; Kalathur
dc.creatorRavi K.; Povoa
dc.creatorVanda; Ribeiro
dc.creatorAna R.; Brandalise
dc.creatorSilvia R.; Dejardin
dc.creatorEmmanuel; Alves
dc.creatorNuno L.; Ghysdael
dc.creatorJacques; Barata
dc.creatorJoao T.; Yunes
dc.creatorJose Andres; dos Santos
dc.creatorNuno R.
dc.date2015-DEC
dc.date2016-06-07T13:35:15Z
dc.date2016-06-07T13:35:15Z
dc.date.accessioned2018-03-29T01:50:48Z
dc.date.available2018-03-29T01:50:48Z
dc.identifier
dc.identifierLymphotoxin-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.
dc.identifier0007-1048
dc.identifierWOS:000367741400007
dc.identifier10.1111/bjh.13760
dc.identifierhttp://onlinelibrary.wiley.com/doi/10.1111/bjh.13760/epdf
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/244086
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1307784
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionLymphotoxin-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.
dc.description171
dc.description5
dc.description
dc.description736
dc.description751
dc.descriptionFundacao para a Ciencia e a Tecnologia [PTDC/SAU-OBD/103336/2008, PEst-OE/EQB/LA0023/2013]
dc.descriptionNucleo Regional Sul da Liga Portuguesa Contra o Cancro (NRS/LPCC-Terry Fox)
dc.descriptionFundacao MSD
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionPlan Cancer Action 29
dc.descriptionFCT [SFRH/BD/75137/2010, SFRH/BD/80503/2011, SFRH/BPD/70718/2010, IF/00056/2012]
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFCT Ciencia
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description
dc.description
dc.description
dc.languageen
dc.publisherWILEY-BLACKWELL
dc.publisher
dc.publisherHOBOKEN
dc.relationBRITISH JOURNAL OF HAEMATOLOGY
dc.rightsfechado
dc.sourceWOS
dc.subjectNf-kappa-b
dc.subjectTumor-necrosis-factor
dc.subjectThymic Stromal Cells
dc.subjectGene-expression
dc.subjectMolecular-genetics
dc.subjectLymphoid-tissues
dc.subjectProstate-cancer
dc.subjectThymocytes
dc.subjectPathway
dc.subjectAlpha
dc.titleLymphotoxin-beta Receptor In Microenvironmental Cells Promotes The Development Of T-cell Acute Lymphoblastic Leukaemia With Cortical/mature Immunophenotype
dc.typeArtículos de revistas


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