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IL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: an update

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dc.contributor.authorOliveira, Mariana L.
dc.contributor.authorAkkapeddi, Padma
dc.contributor.authorRibeiro, Daniel
dc.contributor.authorMelão, Alice
dc.contributor.authorBarata, João T.
dc.date.accessioned2022-04-12T13:45:44Z
dc.date.available2022-04-12T13:45:44Z
dc.date.issued2019
dc.description© 2018 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/)pt_PT
dc.description.abstractInterleukin 7 (IL-7) and its receptor (IL-7R, a heterodimer of IL-7Rα and γc) are essential for normal lymphoid development. In their absence, severe combined immunodeficiency occurs. By contrast, excessive IL-7/IL-7R-mediated signaling can drive lymphoid leukemia development, disease acceleration and resistance to chemotherapy. IL-7 and IL-7R activate three main pathways: STAT5, PI3K/Akt/mTOR and MEK/Erk, ultimately leading to the promotion of leukemia cell viability, cell cycle progression and growth. However, the contribution of each of these pathways towards particular functional outcomes is still not completely known and appears to differ between normal and malignant states. For example, IL-7 upregulates Bcl-2 in a PI3K/Akt/mTOR-dependent and STAT5-independent manner in T-ALL cells. This is a 'symmetric image' of what apparently happens in normal lymphoid cells, where PI3K/Akt/mTOR does not impact on Bcl-2 and regulates proliferation rather than survival. In this review, we provide an updated summary of the knowledge on IL-7/IL-7R-mediated signaling in the context of cancer, focusing mainly on T-cell acute lymphoblastic leukemia, where this axis has been more extensively studied.pt_PT
dc.description.sponsorshipPublication costs were supported by LISBOA-01-0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa2020 Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia (FCT, Portugal). The research work in JTB's lab related to the present review was supported by the grants FAPESP/20015/2014 and PTDC/MEC-HEM/31588/2017, from FCT; and by the consolidator grant ERC CoG-648455 from the European Research Council, under the European Union's Horizon 2020 research and innovation programme. JTB is an FCT investigator (consolidator). MLO is a LisbonBioMed PhD student and received a fellowship from FCT. PA received a PhD fellowship from the EU Marie Sklodowska-Curie ITN Protein Conjugates.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAdv Biol Regul. 2019 Jan;71:88-96pt_PT
dc.identifier.doi10.1016/j.jbior.2018.09.012pt_PT
dc.identifier.eissn2212-4934
dc.identifier.issn2212-4926
dc.identifier.urihttp://hdl.handle.net/10451/52303
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationLISBOA-01-0145-FEDER-007391pt_PT
dc.relationIL-7/IL-7R signaling networks in health and malignancy
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/advances-in-biological-regulationpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectB-cell acute lymphoblastic leukemiapt_PT
dc.subjectIL-7Rpt_PT
dc.subjectInterleukin 7pt_PT
dc.subjectJAK/STAT pathwaypt_PT
dc.subjectPI3K/Akt/mTOR pathwaypt_PT
dc.subjectT-ALLpt_PT
dc.subjectT-cell acute lymphoblastic leukemiapt_PT
dc.titleIL-7R-mediated signaling in T-cell acute lymphoblastic leukemia: an updatept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberFAPESP/20015/2014
oaire.awardNumberPTDC/MEC-HEM/31588/2017
oaire.awardNumber648455
oaire.awardTitleIL-7/IL-7R signaling networks in health and malignancy
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/FAPESP%2F20015%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FMEC-HEM%2F31588%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/648455/EU
oaire.citation.endPage96pt_PT
oaire.citation.startPage88pt_PT
oaire.citation.titleAdvances in Biological Regulationpt_PT
oaire.citation.volume71pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStream9471 - RIDTI
oaire.fundingStreamH2020
person.familyNameAkkapeddi
person.familyNameSilva Ribeiro
person.familyNameMelão
person.familyNameBarata
person.givenNamePadma
person.givenNameDaniel Filipe
person.givenNameAlice
person.givenNameJoão
person.identifier.ciencia-id7016-104B-7CE8
person.identifier.ciencia-id5B17-5400-736D
person.identifier.orcid0000-0002-4012-9568
person.identifier.orcid0000-0003-3660-9646
person.identifier.orcid0000-0001-5629-7796
person.identifier.orcid0000-0002-4826-8976
person.identifier.ridD-9181-2015
person.identifier.scopus-author-id37038033200
person.identifier.scopus-author-id7006937224
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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