Mutant IL7R collaborates with MYC to induce T-cell acute lymphoblastic leukemia
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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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 |
format |
article |
status_str |
publishedVersion |
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 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 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 |
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 |
mluisa.alvim@gmail.com |
_version_ |
1817545875610664960 |