An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor 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/10451/51189 |
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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
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An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.Kinase signaling fuels growth of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet its role in leukemia initiation is unclear and has not been shown in primary human hematopoietic cells. We previously described activating mutations in interleukin-7 receptor alpha (IL7RA) in poor-prognosis "ph-like" BCP-ALL. Here we show that expression of activated mutant IL7RA in human CD34+ hematopoietic stem and progenitor cells induces a preleukemic state in transplanted immunodeficient NOD/LtSz-scid IL2Rγnull mice, characterized by persistence of self-renewing Pro-B cells with non-productive V(D)J gene rearrangements. Preleukemic CD34+CD10highCD19+ cells evolve into BCP-ALL with spontaneously acquired Cyclin Dependent Kinase Inhibitor 2 A (CDKN2A) deletions, as commonly observed in primary human BCP-ALL. CRISPR mediated gene silencing of CDKN2A in primary human CD34+ cells transduced with activated IL7RA results in robust development of BCP-ALLs in-vivo. Thus, we demonstrate that constitutive activation of IL7RA can initiate preleukemia in primary human hematopoietic progenitors and cooperates with CDKN2A silencing in progression into BCP-ALL.This work was supported by the Israel Science Foundation (# 1178/12 to S.I.), Children with Cancer (UK) (S.I. and T.E.), Swiss Bridge Foundation (S.I.), WLBH Foundation (S.I.), Waxman Cancer Research Foundation (S.I.), US–Israel Binational Science Foundation, Israeli health ministry ERA-NET program (#CANCER11-FP-127 to S.I.), Hans Neufeld Stiftung, the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope (S.I. grants # 00161), the Nevzlin Genomic Center for Precision Medicine in Schneider Children’s Medical Center of Israel, The European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 813091 (S.I.) and the Israel Childhood Cancer Foundation (S.I.). I.G. was partially supported by Israeli ministry of Immigrant Absorption.Springer NatureRepositório da Universidade de LisboaGeron, IfatSavino, Angela MariaFishman, HilaTal, NoaBrown, JohnTurati, Virginia A.James, ChelaSarno, JolandaHameiri-Grossman, MichalLee, Yu NeeRein, AvigailManiriho, HillaryBirger, YehuditZemlyansky, AnnaMuler, InnaDavis, Kara L.Marcu-Malina, VictoriaMattson, NicoleParnas, OrenWagener, RabeaFischer, UteBarata, João T.Jamieson, Catriona H. M.Müschen, MarkusChen, Chun-WeiBorkhardt, ArndtKirsch, Ilan RichardNagler, ArnonEnver, TariqIzraeli, Shai2022-02-09T15:08:04Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51189engNat Commun. 2022 Feb 3;13(1):659.10.1038/s41467-022-28218-72041-1723info: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:RCAAP2023-11-08T16:55:44Zoai:repositorio.ul.pt:10451/51189Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:31.599773Repositório 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 |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
title |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
spellingShingle |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia Geron, Ifat |
title_short |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
title_full |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
title_fullStr |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
title_full_unstemmed |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
title_sort |
An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia |
author |
Geron, Ifat |
author_facet |
Geron, Ifat Savino, Angela Maria Fishman, Hila Tal, Noa Brown, John Turati, Virginia A. James, Chela Sarno, Jolanda Hameiri-Grossman, Michal Lee, Yu Nee Rein, Avigail Maniriho, Hillary Birger, Yehudit Zemlyansky, Anna Muler, Inna Davis, Kara L. Marcu-Malina, Victoria Mattson, Nicole Parnas, Oren Wagener, Rabea Fischer, Ute Barata, João T. Jamieson, Catriona H. M. Müschen, Markus Chen, Chun-Wei Borkhardt, Arndt Kirsch, Ilan Richard Nagler, Arnon Enver, Tariq Izraeli, Shai |
author_role |
author |
author2 |
Savino, Angela Maria Fishman, Hila Tal, Noa Brown, John Turati, Virginia A. James, Chela Sarno, Jolanda Hameiri-Grossman, Michal Lee, Yu Nee Rein, Avigail Maniriho, Hillary Birger, Yehudit Zemlyansky, Anna Muler, Inna Davis, Kara L. Marcu-Malina, Victoria Mattson, Nicole Parnas, Oren Wagener, Rabea Fischer, Ute Barata, João T. Jamieson, Catriona H. M. Müschen, Markus Chen, Chun-Wei Borkhardt, Arndt Kirsch, Ilan Richard Nagler, Arnon Enver, Tariq Izraeli, Shai |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Geron, Ifat Savino, Angela Maria Fishman, Hila Tal, Noa Brown, John Turati, Virginia A. James, Chela Sarno, Jolanda Hameiri-Grossman, Michal Lee, Yu Nee Rein, Avigail Maniriho, Hillary Birger, Yehudit Zemlyansky, Anna Muler, Inna Davis, Kara L. Marcu-Malina, Victoria Mattson, Nicole Parnas, Oren Wagener, Rabea Fischer, Ute Barata, João T. Jamieson, Catriona H. M. Müschen, Markus Chen, Chun-Wei Borkhardt, Arndt Kirsch, Ilan Richard Nagler, Arnon Enver, Tariq Izraeli, Shai |
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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-02-09T15:08:04Z 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/10451/51189 |
url |
http://hdl.handle.net/10451/51189 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Nat Commun. 2022 Feb 3;13(1):659. 10.1038/s41467-022-28218-7 2041-1723 |
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openAccess |
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Springer Nature |
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Springer Nature |
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