The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways

Detalhes bibliográficos
Autor(a) principal: Cardoso, Bruno A
Data de Publicação: 2015
Outros Autores: Belo, Hélio, Barata, João T, Almeida, António M
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/21495
Resumo: This study was funded by research grants from "Instituto Portugues de Oncologia de Lisboa-Francisco Gentil" (IPOL-FG), "Associacao Portuguesa Contra a Leucemia" (APCL) and "Liga Portuguesa Contra o Cancro" (LPCC). BAC is a recipient of a Post-Doc fellowship from "Fundacao para a Ciencia e Tecnologia" (FCT-SFRH/BPD/79209/2011) and HB from LPCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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spelling The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathwaysHISTONE-DEACETYLASE INHIBITORPOLYCYTHEMIA-VERAPRIMARY MYELOFIBROSISMUTATIONESSENTIAL THROMBOCYTHEMIAACUTE LYMPHOBLASTIC-LEUKEMIATYROSINE KINASE JAK2STEM-CELLPHASE-IIPROGENITOR CELLSMultidisciplinary SciencesThis study was funded by research grants from "Instituto Portugues de Oncologia de Lisboa-Francisco Gentil" (IPOL-FG), "Associacao Portuguesa Contra a Leucemia" (APCL) and "Liga Portuguesa Contra o Cancro" (LPCC). BAC is a recipient of a Post-Doc fellowship from "Fundacao para a Ciencia e Tecnologia" (FCT-SFRH/BPD/79209/2011) and HB from LPCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN) are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi), albeit with poorer tolerance. Here, we show that bone marrow (BM) stromal cells (HS-5) protected MPN-derived cell lines (SET-2; HEL and UKE-1) and MPN patient-derived BM cells from the cytotoxic effects of Ruxolitinib and the HDACi Vorinostat. This protective effect was mediated, at least in part, by the secretion of soluble factors from the BM stroma. In addition, it correlated with the activation of signalling pathways important for cellular homeostasis, such as JAK-STAT, PI3K, JNK, MEK-ERK and NF-kappa B. Importantly, the pharmacological inhibition of JNK and PI3K pathways completely abrogated the BM protective effect on MPN cell lines and MPN patient samples. Our findings shed light on mechanisms of tumour survival and may indicate novel therapeutic approaches for the treatment of MPN.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNCardoso, Bruno ABelo, HélioBarata, João TAlmeida, António M2017-06-08T22:01:30Z2015-12-012015-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/21495eng1932-6203PURE: 514120https://doi.org/10.1371/journal.pone.0143897info: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:RCAAP2024-03-11T04:08:14Zoai:run.unl.pt:10362/21495Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:26:49.392201Repositório 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 The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
title The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
spellingShingle The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
Cardoso, Bruno A
HISTONE-DEACETYLASE INHIBITOR
POLYCYTHEMIA-VERA
PRIMARY MYELOFIBROSIS
MUTATION
ESSENTIAL THROMBOCYTHEMIA
ACUTE LYMPHOBLASTIC-LEUKEMIA
TYROSINE KINASE JAK2
STEM-CELL
PHASE-II
PROGENITOR CELLS
Multidisciplinary Sciences
title_short The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
title_full The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
title_fullStr The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
title_full_unstemmed The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
title_sort The bone marrow-mediated protection of myeloproliferative neoplastic cells to Vorinostat and Ruxolitinib relies on the activation of JNK and PI3K signalling pathways
author Cardoso, Bruno A
author_facet Cardoso, Bruno A
Belo, Hélio
Barata, João T
Almeida, António M
author_role author
author2 Belo, Hélio
Barata, João T
Almeida, António M
author2_role author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Cardoso, Bruno A
Belo, Hélio
Barata, João T
Almeida, António M
dc.subject.por.fl_str_mv HISTONE-DEACETYLASE INHIBITOR
POLYCYTHEMIA-VERA
PRIMARY MYELOFIBROSIS
MUTATION
ESSENTIAL THROMBOCYTHEMIA
ACUTE LYMPHOBLASTIC-LEUKEMIA
TYROSINE KINASE JAK2
STEM-CELL
PHASE-II
PROGENITOR CELLS
Multidisciplinary Sciences
topic HISTONE-DEACETYLASE INHIBITOR
POLYCYTHEMIA-VERA
PRIMARY MYELOFIBROSIS
MUTATION
ESSENTIAL THROMBOCYTHEMIA
ACUTE LYMPHOBLASTIC-LEUKEMIA
TYROSINE KINASE JAK2
STEM-CELL
PHASE-II
PROGENITOR CELLS
Multidisciplinary Sciences
description This study was funded by research grants from "Instituto Portugues de Oncologia de Lisboa-Francisco Gentil" (IPOL-FG), "Associacao Portuguesa Contra a Leucemia" (APCL) and "Liga Portuguesa Contra o Cancro" (LPCC). BAC is a recipient of a Post-Doc fellowship from "Fundacao para a Ciencia e Tecnologia" (FCT-SFRH/BPD/79209/2011) and HB from LPCC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
publishDate 2015
dc.date.none.fl_str_mv 2015-12-01
2015-12-01T00:00:00Z
2017-06-08T22:01:30Z
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/10362/21495
url http://hdl.handle.net/10362/21495
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
PURE: 514120
https://doi.org/10.1371/journal.pone.0143897
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
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
instname_str 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
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