Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia

Detalhes bibliográficos
Autor(a) principal: Oliveira, Mariana L.
Data de Publicação: 2022
Outros Autores: Veloso, Alexandra, Garcia, Elaine G., Iyer, Sowmya, Pereira, Clara, Barreto, Vasco M., Langenau, David M., 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/10362/142073
Resumo: Funding Information: This work was supported by NIH grant R01CA211734 (DML), the MGH Research Scholar Award (DML), the ERC consolidator CoG-648455 and proof-of-concept PoC-862545 grants from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme (JTB), and the FCT grants FAPESP/20015/2014, PTDC/MEC-HEM/31588/2017 and PTDC/MEC-ONC/4606/2021 (JTB).
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spelling Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemiaHematologyOncologyCancer ResearchSDG 3 - Good Health and Well-beingFunding Information: This work was supported by NIH grant R01CA211734 (DML), the MGH Research Scholar Award (DML), the ERC consolidator CoG-648455 and proof-of-concept PoC-862545 grants from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme (JTB), and the FCT grants FAPESP/20015/2014, PTDC/MEC-HEM/31588/2017 and PTDC/MEC-ONC/4606/2021 (JTB).T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive pediatric cancer. Amongst the wide array of driver mutations, 10% of T-ALL patients display gain-of-function mutations in the IL-7 receptor α chain (IL-7Rα, encoded by IL7R), which occur in different molecular subtypes of this disease. However, it is still unclear whether IL-7R mutational activation is sufficient to transform T-cell precursors. Also, which genes cooperate with IL7R to drive leukemogenesis remain poorly defined. Here, we demonstrate that mutant IL7R alone is capable of inducing T-ALL with long-latency in stable transgenic zebrafish and transformation is associated with MYC transcriptional activation. Additionally, we find that mutant IL7R collaborates with Myc to induce early onset T-ALL in transgenic zebrafish, supporting a model where these pathways collaborate to drive leukemogenesis. T-ALLs co-expressing mutant IL7R and Myc activate STAT5 and AKT pathways, harbor reduced numbers of apoptotic cells and remake tumors in transplanted zebrafish faster than T-ALLs expressing Myc alone. Moreover, limiting-dilution cell transplantation experiments reveal that activated IL-7R signaling increases the overall frequency of leukemia propagating cells. Our work highlights a synergy between mutant IL7R and Myc in inducing T-ALL and demonstrates that mutant IL7R enriches for leukemia propagating potential.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNOliveira, Mariana L.Veloso, AlexandraGarcia, Elaine G.Iyer, SowmyaPereira, ClaraBarreto, Vasco M.Langenau, David M.Barata, João T.2022-07-18T22:27:17Z2022-05-172022-05-17T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://hdl.handle.net/10362/142073eng0887-6924PURE: 45374300https://doi.org/10.1038/s41375-022-01590-5info: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:RCAAP2024-05-22T18:03:33Zoai:run.unl.pt:10362/142073Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:03:33Repositório 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 Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
title Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
spellingShingle Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
Oliveira, Mariana L.
Hematology
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
title_short Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
title_full Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
title_fullStr Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
title_full_unstemmed Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
title_sort Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
author Oliveira, Mariana L.
author_facet Oliveira, Mariana L.
Veloso, Alexandra
Garcia, Elaine G.
Iyer, Sowmya
Pereira, Clara
Barreto, Vasco M.
Langenau, David M.
Barata, João T.
author_role author
author2 Veloso, Alexandra
Garcia, Elaine G.
Iyer, Sowmya
Pereira, Clara
Barreto, Vasco M.
Langenau, David M.
Barata, João T.
author2_role author
author
author
author
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 Oliveira, Mariana L.
Veloso, Alexandra
Garcia, Elaine G.
Iyer, Sowmya
Pereira, Clara
Barreto, Vasco M.
Langenau, David M.
Barata, João T.
dc.subject.por.fl_str_mv Hematology
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
topic Hematology
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
description Funding Information: This work was supported by NIH grant R01CA211734 (DML), the MGH Research Scholar Award (DML), the ERC consolidator CoG-648455 and proof-of-concept PoC-862545 grants from the European Research Council, under the European Union’s Horizon 2020 research and innovation programme (JTB), and the FCT grants FAPESP/20015/2014, PTDC/MEC-HEM/31588/2017 and PTDC/MEC-ONC/4606/2021 (JTB).
publishDate 2022
dc.date.none.fl_str_mv 2022-07-18T22:27:17Z
2022-05-17
2022-05-17T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/142073
url http://hdl.handle.net/10362/142073
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0887-6924
PURE: 45374300
https://doi.org/10.1038/s41375-022-01590-5
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eu_rights_str_mv openAccess
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application/pdf
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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
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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