Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells

Detalhes bibliográficos
Autor(a) principal: Pereira, Olga
Data de Publicação: 2018
Outros Autores: Teixeira, Alexandra, Marques, Maria Belém Sousa Sampaio, Castro, Isabel, Girão, Henrique, Ludovico, Paula
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/58061
Resumo: Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.
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spelling Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cellsacute myeloid leukaemiaautophagyenergetic metabolismglycolysismitochondrial oxidative phosphorylationnutrient-sensing pathwaysCiências Médicas::Medicina BásicaScience & TechnologyAcute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.This work was developed under the scope of the project NORTE‐01‐0145‐FEDER‐000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER), and by FEDER, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI‐01‐0145‐FEDER‐007038. OP and BSM are supported by fellowships from the Fundação para a Ciência e Tecnologia (FCT, Portugal) (SFRH/BD/52292/2013 and SFRH/BPD/90533/2012, respectively)info:eu-repo/semantics/publishedVersionBlackwell Publishing Inc.Universidade do MinhoPereira, OlgaTeixeira, AlexandraMarques, Maria Belém Sousa SampaioCastro, IsabelGirão, HenriqueLudovico, Paula2018-102018-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/58061engPereira O, Teixeira A, Sampaio-Marques B, Castro I, Gir ~ ao H, Ludovico P. Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells. J Cell Mol Med . 2018;22:4807 – 4817. https://doi.org/10.1111/jcmm.137371582-18381582-493410.1111/jcmm.1373730117681https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.13737info: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:RCAAP2023-07-21T12:13:46Zoai:repositorium.sdum.uminho.pt:1822/58061Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:05:56.346025Repositório 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 Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
title Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
spellingShingle Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
Pereira, Olga
acute myeloid leukaemia
autophagy
energetic metabolism
glycolysis
mitochondrial oxidative phosphorylation
nutrient-sensing pathways
Ciências Médicas::Medicina Básica
Science & Technology
title_short Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
title_full Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
title_fullStr Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
title_full_unstemmed Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
title_sort Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells
author Pereira, Olga
author_facet Pereira, Olga
Teixeira, Alexandra
Marques, Maria Belém Sousa Sampaio
Castro, Isabel
Girão, Henrique
Ludovico, Paula
author_role author
author2 Teixeira, Alexandra
Marques, Maria Belém Sousa Sampaio
Castro, Isabel
Girão, Henrique
Ludovico, Paula
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Pereira, Olga
Teixeira, Alexandra
Marques, Maria Belém Sousa Sampaio
Castro, Isabel
Girão, Henrique
Ludovico, Paula
dc.subject.por.fl_str_mv acute myeloid leukaemia
autophagy
energetic metabolism
glycolysis
mitochondrial oxidative phosphorylation
nutrient-sensing pathways
Ciências Médicas::Medicina Básica
Science & Technology
topic acute myeloid leukaemia
autophagy
energetic metabolism
glycolysis
mitochondrial oxidative phosphorylation
nutrient-sensing pathways
Ciências Médicas::Medicina Básica
Science & Technology
description Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic neoplasms characterized by diverse combinations of genetic, phenotypic and clinical features representing a major challenge for the development of targeted therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient-sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer cells, including AML cells, survival and proliferation. Nevertheless, the role of these metabolic adaptations on the AML pathogenesis is still controversial. In this work, the metabolic status and the respective metabolic networks operating in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and survival was characterized. Data show that whereas KG-1 cells exhibited preferential mitochondrial oxidative phosphorylation metabolism with constitutive co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL-60 cells displayed a dependent glycolytic profile mainly associated with AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a promising therapeutical target in some scenarios while inhibition of AMPK and mTORC1 has no major impact on KG-1 cells' survival. The results highlight an exclusive metabolic profile for each tested AML cells and its impact on determination of the anti-leukaemia efficacy and on personalized combinatory therapy with conventional and targeted agents.
publishDate 2018
dc.date.none.fl_str_mv 2018-10
2018-10-01T00:00:00Z
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/1822/58061
url http://hdl.handle.net/1822/58061
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Pereira O, Teixeira A, Sampaio-Marques B, Castro I, Gir ~ ao H, Ludovico P. Signalling mechanisms that regulate metabolic profile and autophagy of acute myeloid leukaemia cells. J Cell Mol Med . 2018;22:4807 – 4817. https://doi.org/10.1111/jcmm.13737
1582-1838
1582-4934
10.1111/jcmm.13737
30117681
https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.13737
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.publisher.none.fl_str_mv Blackwell Publishing Inc.
publisher.none.fl_str_mv Blackwell Publishing Inc.
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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