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/10451/53323
Resumo: © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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spelling Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.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.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)Springer NatureRepositório da Universidade de LisboaOliveira, Mariana L.Veloso, AlexandraGarcia, Elaine G.Iyer, SowmyaPereira, ClaraBarreto, Vasco M.Langenau, David M.Barata, João T.2022-06-07T15:31:45Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53323engLeukemia. 2022 Jun;36(6):1533-15400887-692410.1038/s41375-022-01590-51476-5551info: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:RCAAP2023-11-08T16:59:02Zoai:repositorio.ul.pt:10451/53323Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:17.265361Repositório 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.
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 Repositório da Universidade de Lisboa
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.
description © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-07T15:31:45Z
2022
2022-01-01T00:00:00Z
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/10451/53323
url http://hdl.handle.net/10451/53323
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Leukemia. 2022 Jun;36(6):1533-1540
0887-6924
10.1038/s41375-022-01590-5
1476-5551
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 Springer Nature
publisher.none.fl_str_mv Springer Nature
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
repository.mail.fl_str_mv
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