Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels

Detalhes bibliográficos
Autor(a) principal: Gomes, Ana Margarida
Data de Publicação: 2014
Outros Autores: Soares, Maria Vieira, Ribeiro, Patrícia, Caldas, Joana, Póvoa, Vanda, Martins, Leila, Melão, Alice, Serra-Caetano, Ana, de Sousa, Aida B., Lacerda, João, Barata, João T.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/51175
Resumo: © 2014 Ferrata Storti Foundation. This is an open-access paper
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spelling Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels© 2014 Ferrata Storti Foundation. This is an open-access paperAdult B-cell acute lymphoblastic leukemia remains a major therapeutic challenge, requiring a better characterization of the molecular determinants underlying disease progression and resistance to treatment. Here, using a phospho-flow cytometry approach we show that adult diagnostic B-cell acute lymphoblastic leukemia specimens display PI3K/Akt pathway hyperactivation, irrespective of their BCR-ABL status and despite paradoxically high basal expression of PTEN, the major negative regulator of the pathway. Protein kinase CK2 is known to phosphorylate PTEN thereby driving PTEN protein stabilization and concomitant PTEN functional inactivation. In agreement, we found that adult B-cell acute lymphoblastic leukemia samples show significantly higher CK2 kinase activity and lower PTEN lipid phosphatase activity than healthy controls. Moreover, the clinical-grade CK2 inhibitor CX-4945 (Silmitasertib) reversed PTEN levels in leukemia cells to those observed in healthy controls, and promoted leukemia cell death without significantly affecting normal bone marrow cells. Our studies indicate that CK2-mediated PTEN posttranslational inactivation, associated with PI3K/Akt pathway hyperactivation, are a common event in adult B-cell acute lymphoblastic leukemia and suggest that CK2 inhibition may constitute a valid, novel therapeutic tool in this malignancy.This study was supported by grant PTDC/IC/83023/2007, from Fundação para a Ciência e a Tecnologia (FCT). A.M.G. and V.P. received BI fellowships from FCT. L.R.M. and A.M. received a post-doctoral and a PhD fellowship, respectively, both from FCT.Repositório da Universidade de LisboaGomes, Ana MargaridaSoares, Maria VieiraRibeiro, PatríciaCaldas, JoanaPóvoa, VandaMartins, LeilaMelão, AliceSerra-Caetano, Anade Sousa, Aida B.Lacerda, JoãoBarata, João T.2022-02-08T17:16:32Z20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51175engHaematologica. 2014 Jun; 99(6): 1062-1068.0390-607810.3324/haematol.2013.0964381592-8721info: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:RCAAP2023-11-08T16:55:42Zoai:repositorio.ul.pt:10451/51175Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:28.938021Repositório 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 Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
title Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
spellingShingle Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
Gomes, Ana Margarida
title_short Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
title_full Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
title_fullStr Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
title_full_unstemmed Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
title_sort Adult B-cell acute lymphoblastic leukemia cells display decreased PTEN activity and constitutive hyperactivation of PI3K/Akt pathway despite high PTEN protein levels
author Gomes, Ana Margarida
author_facet Gomes, Ana Margarida
Soares, Maria Vieira
Ribeiro, Patrícia
Caldas, Joana
Póvoa, Vanda
Martins, Leila
Melão, Alice
Serra-Caetano, Ana
de Sousa, Aida B.
Lacerda, João
Barata, João T.
author_role author
author2 Soares, Maria Vieira
Ribeiro, Patrícia
Caldas, Joana
Póvoa, Vanda
Martins, Leila
Melão, Alice
Serra-Caetano, Ana
de Sousa, Aida B.
Lacerda, João
Barata, João T.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Gomes, Ana Margarida
Soares, Maria Vieira
Ribeiro, Patrícia
Caldas, Joana
Póvoa, Vanda
Martins, Leila
Melão, Alice
Serra-Caetano, Ana
de Sousa, Aida B.
Lacerda, João
Barata, João T.
description © 2014 Ferrata Storti Foundation. This is an open-access paper
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-01-01T00:00:00Z
2022-02-08T17:16:32Z
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/10451/51175
url http://hdl.handle.net/10451/51175
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Haematologica. 2014 Jun; 99(6): 1062-1068.
0390-6078
10.3324/haematol.2013.096438
1592-8721
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
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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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