An instructive role for Interleukin-7 receptor α in the development of human B-cell precursor leukemia

Detalhes bibliográficos
Autor(a) principal: Geron, Ifat
Data de Publicação: 2022
Outros Autores: 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
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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spelling 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
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author
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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
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