NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.1/14394 |
Resumo: | Activation of the receptor activator of nuclear factor-kappa B (RANK) by its ligand (RANKL) is involved in both solid and hematological malignancies, including multiple myeloma, acute myeloid leukemia and B-cell leukemia. Although RANKL expression has been described in normal T cells, a potential role in T-cell leukemia remains undefined. Here, we used a model of immature T-cell leukemia/lymphoma, the TEL-JAK2 transgenic mice, to assess RANKL expression in leukemic cells and its regulatory mechanisms. We found that Rankl mRNA was significantly overexpressed in leukemic T cells when compared to wild-type thymocytes, their nonmalignant counterparts. Moreover, Rankl mRNA and RANKL surface expression in leukemic cells was induced by T-cell receptor (TCR) signaling activation, dependently on the NFKB signaling pathway. These results indicate that TCR-activated leukemic T cells express high levels of RANKL and are potential inducers of RANK signaling in microenvironmental cells. (C) 2019 Elsevier Inc. All rights reserved. |
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NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemiaFactor receptor familyOsteoclast differentiationOsteoprotegerin-ligandEpithelial-cellsActivatorCytokineTranceGrowthMemberMechanismsActivation of the receptor activator of nuclear factor-kappa B (RANK) by its ligand (RANKL) is involved in both solid and hematological malignancies, including multiple myeloma, acute myeloid leukemia and B-cell leukemia. Although RANKL expression has been described in normal T cells, a potential role in T-cell leukemia remains undefined. Here, we used a model of immature T-cell leukemia/lymphoma, the TEL-JAK2 transgenic mice, to assess RANKL expression in leukemic cells and its regulatory mechanisms. We found that Rankl mRNA was significantly overexpressed in leukemic T cells when compared to wild-type thymocytes, their nonmalignant counterparts. Moreover, Rankl mRNA and RANKL surface expression in leukemic cells was induced by T-cell receptor (TCR) signaling activation, dependently on the NFKB signaling pathway. These results indicate that TCR-activated leukemic T cells express high levels of RANKL and are potential inducers of RANK signaling in microenvironmental cells. (C) 2019 Elsevier Inc. All rights reserved.Fundacao para a Ciencia e a Tecnologia (Portugal)Portuguese Foundation for Science and Technology [PTDC/SAU-OBD/103336/2008, UID/BIM/04773/2013, POCI-01-0145-FEDER-007274, SFRH/BD/75137/2010, IF/00056/2012]European Regional Development Fund through COMPETE 2020 programEuropean Union (EU) [NORTE-01-0145-FEDER-000029]Academic Press Inc Elsevier ScienceSapientiaFernandes, Mónica TCaroco, Lara S.Pacheco-Leyva, IvetteR. dos Santos, Nuno2020-07-24T10:52:42Z2019-032019-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10400.1/14394eng0006-291X10.1016/j.bbrc.2019.01.089info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:26:41Zoai:sapientia.ualg.pt:10400.1/14394Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:05:24.358819Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
title |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
spellingShingle |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia Fernandes, Mónica T Factor receptor family Osteoclast differentiation Osteoprotegerin-ligand Epithelial-cells Activator Cytokine Trance Growth Member Mechanisms |
title_short |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
title_full |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
title_fullStr |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
title_full_unstemmed |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
title_sort |
NF-kappa B-dependent RANKL expression in a mouse model of immature T-cell leukemia |
author |
Fernandes, Mónica T |
author_facet |
Fernandes, Mónica T Caroco, Lara S. Pacheco-Leyva, Ivette R. dos Santos, Nuno |
author_role |
author |
author2 |
Caroco, Lara S. Pacheco-Leyva, Ivette R. dos Santos, Nuno |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Sapientia |
dc.contributor.author.fl_str_mv |
Fernandes, Mónica T Caroco, Lara S. Pacheco-Leyva, Ivette R. dos Santos, Nuno |
dc.subject.por.fl_str_mv |
Factor receptor family Osteoclast differentiation Osteoprotegerin-ligand Epithelial-cells Activator Cytokine Trance Growth Member Mechanisms |
topic |
Factor receptor family Osteoclast differentiation Osteoprotegerin-ligand Epithelial-cells Activator Cytokine Trance Growth Member Mechanisms |
description |
Activation of the receptor activator of nuclear factor-kappa B (RANK) by its ligand (RANKL) is involved in both solid and hematological malignancies, including multiple myeloma, acute myeloid leukemia and B-cell leukemia. Although RANKL expression has been described in normal T cells, a potential role in T-cell leukemia remains undefined. Here, we used a model of immature T-cell leukemia/lymphoma, the TEL-JAK2 transgenic mice, to assess RANKL expression in leukemic cells and its regulatory mechanisms. We found that Rankl mRNA was significantly overexpressed in leukemic T cells when compared to wild-type thymocytes, their nonmalignant counterparts. Moreover, Rankl mRNA and RANKL surface expression in leukemic cells was induced by T-cell receptor (TCR) signaling activation, dependently on the NFKB signaling pathway. These results indicate that TCR-activated leukemic T cells express high levels of RANKL and are potential inducers of RANK signaling in microenvironmental cells. (C) 2019 Elsevier Inc. All rights reserved. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-03 2019-03-01T00:00:00Z 2020-07-24T10:52:42Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/14394 |
url |
http://hdl.handle.net/10400.1/14394 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0006-291X 10.1016/j.bbrc.2019.01.089 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Academic Press Inc Elsevier Science |
publisher.none.fl_str_mv |
Academic Press Inc Elsevier Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799133294043856896 |