Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH)
Abstract 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 hist...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-08-01
|
Series: | Experimental Hematology & Oncology |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s40164-019-0142-0 |
id |
doaj-fdd73b3c99e543de8590b93dcb95df9c |
---|---|
record_format |
Article |
spelling |
doaj-fdd73b3c99e543de8590b93dcb95df9c2020-11-25T03:49:15ZengBMCExperimental Hematology & Oncology2162-36192019-08-01811710.1186/s40164-019-0142-0Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH)Camille Lobry0Ashish Bains1Leah B. Zamechek2Sherif Ibrahim3Iannis Aifantis4David J. Araten5Institut National de la Santé et de la Recherche Medicale (INSERM) U1170, Institut Gustave RoussyPathology and Laboratory Medicine, Temple UniversityColumbia University Medical CenterCairo DiagnosticsDepartment of Pathology, NYU School of MedicineDivision of Hematology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health and the NYU School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s40164-019-0142-0Paroxysmal nocturnal hemoglobinuria (PNH)TET2 geneMyeloproliferative disordersAplastic anemiaSomatic mutations |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Camille Lobry Ashish Bains Leah B. Zamechek Sherif Ibrahim Iannis Aifantis David J. Araten |
spellingShingle |
Camille Lobry Ashish Bains Leah B. Zamechek Sherif Ibrahim Iannis Aifantis David J. Araten Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) Experimental Hematology & Oncology Paroxysmal nocturnal hemoglobinuria (PNH) TET2 gene Myeloproliferative disorders Aplastic anemia Somatic mutations |
author_facet |
Camille Lobry Ashish Bains Leah B. Zamechek Sherif Ibrahim Iannis Aifantis David J. Araten |
author_sort |
Camille Lobry |
title |
Analysis of TET2 mutations in paroxysmal nocturnal hemoglobinuria (PNH) |
title_short |
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_sort |
analysis of tet2 mutations in paroxysmal nocturnal hemoglobinuria (pnh) |
publisher |
BMC |
series |
Experimental Hematology & Oncology |
issn |
2162-3619 |
publishDate |
2019-08-01 |
description |
Abstract 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. |
topic |
Paroxysmal nocturnal hemoglobinuria (PNH) TET2 gene Myeloproliferative disorders Aplastic anemia Somatic mutations |
url |
http://link.springer.com/article/10.1186/s40164-019-0142-0 |
work_keys_str_mv |
AT camillelobry analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh AT ashishbains analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh AT leahbzamechek analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh AT sherifibrahim analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh AT iannisaifantis analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh AT davidjaraten analysisoftet2mutationsinparoxysmalnocturnalhemoglobinuriapnh |
_version_ |
1724496494585708544 |