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Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms
Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bo...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447237/ https://www.ncbi.nlm.nih.gov/pubmed/37550517 http://dx.doi.org/10.1038/s43018-023-00607-x |
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author | Grockowiak, Elodie Korn, Claudia Rak, Justyna Lysenko, Veronika Hallou, Adrien Panvini, Francesca M. Williams, Matthew Fielding, Claire Fang, Zijian Khatib-Massalha, Eman García-García, Andrés Li, Juan Khorshed, Reema A. González-Antón, Sara Baxter, E. Joanna Kusumbe, Anjali Wilkins, Bridget S. Green, Anna Simons, Benjamin D. Harrison, Claire N. Green, Anthony R. Lo Celso, Cristina Theocharides, Alexandre P. A. Méndez-Ferrer, Simón |
author_facet | Grockowiak, Elodie Korn, Claudia Rak, Justyna Lysenko, Veronika Hallou, Adrien Panvini, Francesca M. Williams, Matthew Fielding, Claire Fang, Zijian Khatib-Massalha, Eman García-García, Andrés Li, Juan Khorshed, Reema A. González-Antón, Sara Baxter, E. Joanna Kusumbe, Anjali Wilkins, Bridget S. Green, Anna Simons, Benjamin D. Harrison, Claire N. Green, Anthony R. Lo Celso, Cristina Theocharides, Alexandre P. A. Méndez-Ferrer, Simón |
author_sort | Grockowiak, Elodie |
collection | PubMed |
description | Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes. JAK–STAT signaling differentially regulates CDC42-dependent HSC polarity, niche interaction and mutant cell expansion. Asymmetric HSC distribution causes differential BM niche remodeling: sinusoidal dilation in polycythemia vera and endosteal niche expansion in essential thrombocythemia. MPN development accelerates in a prematurely aged BM microenvironment, suggesting that the specialized niche can modulate mutant cell expansion. Finally, dissimilar HSC-niche interactions underpin variable clinical response to JAK inhibitor. Therefore, HSC-niche interactions influence the expansion rate and therapy response of cells carrying the same clonal hematopoiesis oncogenic driver. |
format | Online Article Text |
id | pubmed-10447237 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-104472372023-08-25 Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms Grockowiak, Elodie Korn, Claudia Rak, Justyna Lysenko, Veronika Hallou, Adrien Panvini, Francesca M. Williams, Matthew Fielding, Claire Fang, Zijian Khatib-Massalha, Eman García-García, Andrés Li, Juan Khorshed, Reema A. González-Antón, Sara Baxter, E. Joanna Kusumbe, Anjali Wilkins, Bridget S. Green, Anna Simons, Benjamin D. Harrison, Claire N. Green, Anthony R. Lo Celso, Cristina Theocharides, Alexandre P. A. Méndez-Ferrer, Simón Nat Cancer Article Aging facilitates the expansion of hematopoietic stem cells (HSCs) carrying clonal hematopoiesis-related somatic mutations and the development of myeloid malignancies, such as myeloproliferative neoplasms (MPNs). While cooperating mutations can cause transformation, it is unclear whether distinct bone marrow (BM) HSC-niches can influence the growth and therapy response of HSCs carrying the same oncogenic driver. Here we found different BM niches for HSCs in MPN subtypes. JAK–STAT signaling differentially regulates CDC42-dependent HSC polarity, niche interaction and mutant cell expansion. Asymmetric HSC distribution causes differential BM niche remodeling: sinusoidal dilation in polycythemia vera and endosteal niche expansion in essential thrombocythemia. MPN development accelerates in a prematurely aged BM microenvironment, suggesting that the specialized niche can modulate mutant cell expansion. Finally, dissimilar HSC-niche interactions underpin variable clinical response to JAK inhibitor. Therefore, HSC-niche interactions influence the expansion rate and therapy response of cells carrying the same clonal hematopoiesis oncogenic driver. Nature Publishing Group US 2023-08-07 2023 /pmc/articles/PMC10447237/ /pubmed/37550517 http://dx.doi.org/10.1038/s43018-023-00607-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Grockowiak, Elodie Korn, Claudia Rak, Justyna Lysenko, Veronika Hallou, Adrien Panvini, Francesca M. Williams, Matthew Fielding, Claire Fang, Zijian Khatib-Massalha, Eman García-García, Andrés Li, Juan Khorshed, Reema A. González-Antón, Sara Baxter, E. Joanna Kusumbe, Anjali Wilkins, Bridget S. Green, Anna Simons, Benjamin D. Harrison, Claire N. Green, Anthony R. Lo Celso, Cristina Theocharides, Alexandre P. A. Méndez-Ferrer, Simón Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title | Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title_full | Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title_fullStr | Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title_full_unstemmed | Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title_short | Different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
title_sort | different niches for stem cells carrying the same oncogenic driver affect pathogenesis and therapy response in myeloproliferative neoplasms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447237/ https://www.ncbi.nlm.nih.gov/pubmed/37550517 http://dx.doi.org/10.1038/s43018-023-00607-x |
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