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Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH)
BACKGROUND: Large clonal populations of cells bearing PIG-A mutations are the sine qua non of PNH, but the PIG-A mutation itself is insufficient for clonal expansion. The association between PNH and aplastic anemia supports the immune escape model, but not all PNH patients demonstrate a history of a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702710/ https://www.ncbi.nlm.nih.gov/pubmed/31453016 http://dx.doi.org/10.1186/s40164-019-0142-0 |
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author | Lobry, Camille Bains, Ashish Zamechek, Leah B. Ibrahim, Sherif Aifantis, Iannis Araten, David J. |
author_facet | Lobry, Camille Bains, Ashish Zamechek, Leah B. Ibrahim, Sherif Aifantis, Iannis Araten, David J. |
author_sort | Lobry, Camille |
collection | PubMed |
description | BACKGROUND: Large clonal populations of cells bearing PIG-A mutations are the sine qua non of PNH, but the PIG-A mutation itself is insufficient for clonal expansion. The association between PNH and aplastic anemia supports the immune escape model, but not all PNH patients demonstrate a history of aplasia; therefore, second genetic hits driving clonal expansion have been postulated. Based on the previous identification of JAK2 mutations in patients with a myeloproliferative/PNH overlap syndrome, we considered TET2 as a candidate gene in which mutations might be contributing to clonal expansion. METHODS: Here we sequenced the TET2 and JAK2 genes in 19 patients with large PNH clones. RESULTS: We found one patient with a novel somatic nonsense mutation in TET2 in multiple hematopoietic lineages, which was detectable upon repeat testing. This patient has had severe thromboses and has relatively higher peripheral blood counts compared with the other patients—but does not have other features of a myeloproliferative neoplasm. CONCLUSIONS: We conclude that mutations in TET2 may contribute to clonal expansion in exceptional cases of PNH. |
format | Online Article Text |
id | pubmed-6702710 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-67027102019-08-26 Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) Lobry, Camille Bains, Ashish Zamechek, Leah B. Ibrahim, Sherif Aifantis, Iannis Araten, David J. Exp Hematol Oncol Research BACKGROUND: Large clonal populations of cells bearing PIG-A mutations are the sine qua non of PNH, but the PIG-A mutation itself is insufficient for clonal expansion. The association between PNH and aplastic anemia supports the immune escape model, but not all PNH patients demonstrate a history of aplasia; therefore, second genetic hits driving clonal expansion have been postulated. Based on the previous identification of JAK2 mutations in patients with a myeloproliferative/PNH overlap syndrome, we considered TET2 as a candidate gene in which mutations might be contributing to clonal expansion. METHODS: Here we sequenced the TET2 and JAK2 genes in 19 patients with large PNH clones. RESULTS: We found one patient with a novel somatic nonsense mutation in TET2 in multiple hematopoietic lineages, which was detectable upon repeat testing. This patient has had severe thromboses and has relatively higher peripheral blood counts compared with the other patients—but does not have other features of a myeloproliferative neoplasm. CONCLUSIONS: We conclude that mutations in TET2 may contribute to clonal expansion in exceptional cases of PNH. BioMed Central 2019-08-21 /pmc/articles/PMC6702710/ /pubmed/31453016 http://dx.doi.org/10.1186/s40164-019-0142-0 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Lobry, Camille Bains, Ashish Zamechek, Leah B. Ibrahim, Sherif Aifantis, Iannis Araten, David J. Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title | Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_full | Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_fullStr | Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_full_unstemmed | Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_short | Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_sort | analysis of tet2 mutations in paroxysmal nocturnal hemoglobinuria (pnh) |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702710/ https://www.ncbi.nlm.nih.gov/pubmed/31453016 http://dx.doi.org/10.1186/s40164-019-0142-0 |
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