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In utero origin of myelofibrosis presenting in adult monozygotic twins

The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), wi...

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Autores principales: Sousos, Nikolaos, Ní Leathlobhair, Máire, Simoglou Karali, Christina, Louka, Eleni, Bienz, Nicola, Royston, Daniel, Clark, Sally-Ann, Hamblin, Angela, Howard, Kieran, Mathews, Vikram, George, Biju, Roy, Anindita, Psaila, Bethan, Wedge, David C., Mead, Adam J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205768/
https://www.ncbi.nlm.nih.gov/pubmed/35637336
http://dx.doi.org/10.1038/s41591-022-01793-4
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author Sousos, Nikolaos
Ní Leathlobhair, Máire
Simoglou Karali, Christina
Louka, Eleni
Bienz, Nicola
Royston, Daniel
Clark, Sally-Ann
Hamblin, Angela
Howard, Kieran
Mathews, Vikram
George, Biju
Roy, Anindita
Psaila, Bethan
Wedge, David C.
Mead, Adam J.
author_facet Sousos, Nikolaos
Ní Leathlobhair, Máire
Simoglou Karali, Christina
Louka, Eleni
Bienz, Nicola
Royston, Daniel
Clark, Sally-Ann
Hamblin, Angela
Howard, Kieran
Mathews, Vikram
George, Biju
Roy, Anindita
Psaila, Bethan
Wedge, David C.
Mead, Adam J.
author_sort Sousos, Nikolaos
collection PubMed
description The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition. Whole-genome sequencing lineage tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission and subsequent similar disease latency. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. Furthermore, neonatal blood spot analysis confirmed in utero origin of the JAK2V617F mutation in a patient presenting with polycythemia vera (aged 34 years). These findings provide a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs.
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spelling pubmed-92057682022-06-19 In utero origin of myelofibrosis presenting in adult monozygotic twins Sousos, Nikolaos Ní Leathlobhair, Máire Simoglou Karali, Christina Louka, Eleni Bienz, Nicola Royston, Daniel Clark, Sally-Ann Hamblin, Angela Howard, Kieran Mathews, Vikram George, Biju Roy, Anindita Psaila, Bethan Wedge, David C. Mead, Adam J. Nat Med Article The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition. Whole-genome sequencing lineage tracing revealed a common clonal origin of the CALR-mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission and subsequent similar disease latency. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. Furthermore, neonatal blood spot analysis confirmed in utero origin of the JAK2V617F mutation in a patient presenting with polycythemia vera (aged 34 years). These findings provide a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs. Nature Publishing Group US 2022-05-30 2022 /pmc/articles/PMC9205768/ /pubmed/35637336 http://dx.doi.org/10.1038/s41591-022-01793-4 Text en © The Author(s) 2022 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
Sousos, Nikolaos
Ní Leathlobhair, Máire
Simoglou Karali, Christina
Louka, Eleni
Bienz, Nicola
Royston, Daniel
Clark, Sally-Ann
Hamblin, Angela
Howard, Kieran
Mathews, Vikram
George, Biju
Roy, Anindita
Psaila, Bethan
Wedge, David C.
Mead, Adam J.
In utero origin of myelofibrosis presenting in adult monozygotic twins
title In utero origin of myelofibrosis presenting in adult monozygotic twins
title_full In utero origin of myelofibrosis presenting in adult monozygotic twins
title_fullStr In utero origin of myelofibrosis presenting in adult monozygotic twins
title_full_unstemmed In utero origin of myelofibrosis presenting in adult monozygotic twins
title_short In utero origin of myelofibrosis presenting in adult monozygotic twins
title_sort in utero origin of myelofibrosis presenting in adult monozygotic twins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9205768/
https://www.ncbi.nlm.nih.gov/pubmed/35637336
http://dx.doi.org/10.1038/s41591-022-01793-4
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