ArticleThe Journal of clinical investigation2014
Deep sequencing reveals stepwise mutation acquisition in paroxysmal nocturnal hemoglobinuria.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 137 citations in OpenAlex.
- Sustained clonal hematopoiesis by HLA-lacking hematopoietic stem cells without driver mutations in aplastic anemia.Blood advances · 2018Trial
- Lifelong phylogenetic reconstruction of immune-mediated clonal trajectories in paroxysmal nocturnal hemoglobinuria.Leukemia · 2026Article
- Imputing causality and clonal dynamics from single-cell transcriptomics in paroxysmal nocturnal hemoglobinuria.Leukemia · 2026Article
- Analysis of the Recovery of Immune Status in the Patients With Paroxysmal Nocturnal Hemoglobinuria After Treatment With C5 Complement Inhibitor.Journal of clinical laboratory analysis · 2026Article
- High-resolution single-cell mapping of clonal hematopoiesis and structural variation in aplastic anemia.Nature genetics · 2026Article
- Clonal expansion mechanisms in paroxysmal nocturnal hemoglobinuria.International journal of hematology · 2026Review
- Role of NK cells in immune escape in patients with classical paroxysmal nocturnal haemoglobinuria.Clinical and translational medicine · 2025Article
- Diffuse Large B-Cell Lymphoma Combined With Paroxysmal Nocturnal Hemoglobinuria: A Rare Case Report.Clinical case reports · 2025Article
- Cost Comparisons in NICE Technology Appraisals: An External Assessment Group Perspective.PharmacoEconomics · 2025Article
- Low-Allele-Frequency Somatic Variants in a Cohort of Sporadic Saccular "Berry" Cerebral Aneurysms.Journal of the American Heart Association · 2025Article
- PNH clones prevalence study in ph-negative myeloproliferative neoplasms: a multicenter Italian study.Annals of hematology · 2025Observational
- Clinical characteristics and management of paroxysmal nocturnal hemoglobinuria in the Middle East: a narrative review.Clinical and experimental medicine · 2025Review
- Article
- Somatic mutations in Brazilian patients with paroxysmal nocturnal hemoglobinuria: a comprehensive analysis.Frontiers in medicine · 2025Article
- Identifying Genes Associated With Proliferation, Immunity and Thrombosis in Paroxysmal Nocturnal Haemoglobinuria.Journal of cellular and molecular medicine · 2024Article
- Diagnostic landscape of first-time cytometric screening for paroxysmal nocturnal hemoglobinuria in Poland in 2013-2022.Orphanet journal of rare diseases · 2024Article
- Paroxysmal Nocturnal Hemoglobinuria: Biology and Treatment.Medicina (Kaunas, Lithuania) · 2023Review
- Case report: Immune pressure on hematopoietic stem cells can drastically expand glycosylphosphatidylinositol-deficient clones in paroxysmal nocturnal hemoglobinuria.Frontiers in immunology · 2023Article
- Spontaneous Remission in Paroxysmal Nocturnal Hemoglobinuria: An Extremely Rare CaseTurkish journal of haematology : official journal of Turkish Society of Haematology · 2022Article
- A case of postpartum AKI: recurrent atypical hemolytic uremic syndrome, HELLP syndrome or paroxysmal nocturnal hemoglobinuria? Lessons for the clinical nephrologist.Journal of nephrology · 2022Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disease of hematopoietic stem cells that is associated with hemolysis, marrow failure, and thrombophilia. PNH has been considered a monogenic disease that results from somatic mutations in the gene encoding PIGA, which is required for biosynthesis of glycosylphosphatidylinisotol-anchored (GPI-anchored) proteins. The loss of certain GPI-anchored proteins is hypothesized to provide the mutant clone with an extrinsic growth advantage, but some features of PNH argue that there are intrinsic drivers of clonal expansion. Here, we performed whole-exome sequencing of paired PNH+ and PNH- fractions on samples taken from 12 patients as well as targeted deep sequencing of an additional 36 PNH patients. We identified additional somatic mutations that resulted in a complex hierarchical clonal architecture, similar to that observed in myeloid neoplasms. In addition to mutations in PIGA, mutations were found in genes known to be involved in myeloid neoplasm pathogenesis, including TET2, SUZ12, U2AF1, and JAK2. Clonal analysis indicated that these additional mutations arose either as a subclone within the PIGA-mutant population, or prior to PIGA mutation. Together, our data indicate that in addition to PIGA mutations, accessory genetic events are frequent in PNH, suggesting a stepwise clonal evolution derived from a singular stem cell clone.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.