Evidence map›Paper›PMID 42020783›Full record

ArticleLeukemia2026

Imputing causality and clonal dynamics from single-cell transcriptomics in paroxysmal nocturnal hemoglobinuria.

Hiroki Mizumaki, Shouguo Gao, Zhijie Wu, Fernanda Gutierrez-Rodrigues, Lemlem Alemu, Diego Quinones Raffo, Ivana Darden, Olga Rios, Jennifer Lotter, Sachiko Kajigaya and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Hiroki Mizumaki *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9933-4638
Shouguo Gao *Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Zhijie WuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. zhijie.wu@nih.gov.
Fernanda Gutierrez-RodriguesHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0003-3116-4588
Lemlem AlemuHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Diego Quinones RaffoHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Ivana DardenHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Olga RiosHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Jennifer LotterHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Sachiko KajigayaHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Jibran DurraniHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Emma M GroarkeHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-4648-5926
Bhavisha A PatelHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2974-7701
Neal S YoungHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. youngns@nhlbi.nih.gov.ORCID http://orcid.org/0009-0007-0999-2519

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) originates from hematopoietic stem cells (HSCs) harboring somatic mutations in the phosphatidylinositol glycan class A (PIGA) gene. Clonal expansion of PIGA-mutated cells occurs uniquely in the setting of bone marrow (BM) failure, but specific pathophysiologic mechanisms remain unclear. We performed single-cell RNA sequencing (scRNA-seq) of BM cells from patients with large (> 50%) and small (10-50%) PNH cell fractions. In patients with large PNH cell fractions, phenotypically normal hematopoietic stem and progenitor cells (HSPCs) upregulated immune response and apoptosis pathways and downregulated cell-cycling pathways compared with PNH-type HSPCs. BM effector cells upregulated immune response pathways, and cell-cell communication between effector cells and normal HSPCs was greater than in controls. In contrast, in patients with small PNH cell fractions, transcriptional changes in normal HSPCs were reversed: downregulation of immune response pathways and upregulation of the cell-cycling pathways. Notably, transcriptional differences associated with PNH cell fractions were primarily in normal HSCs, whereas PNH-type HSCs showed similar transcriptional profiles between patients with large and small PNH cell fractions. These results implicate immunological negative selection against normal HSCs in PNH. Error-corrected DNA sequencing of patients' blood samples identified multiple PIGA mutations in each patient, consistent with strong selection for the resulting phenotype.

Indexed as

Hemoglobinuria, ParoxysmalSingle-Cell AnalysisTranscriptomeGene Expression ProfilingHematopoietic Stem CellsHumansMembrane ProteinsMutationSingle-Cell Gene Expression AnalysisMembrane Proteinsphosphatidylinositol glycan-class A protein

Identifiers

PMID42020783
PMCPMC13323074

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.