ArticleBlood2021
RUNX-1 haploinsufficiency causes a marked deficiency of megakaryocyte-biased hematopoietic progenitor cells.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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.
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.
Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- CSF1R modulates megakaryopoiesis by targeting RUNX1 in immune thrombocytopenia.Haematologica · 2026Article
- Methylome profiling reveals context-dependent chemo-resistance mechanisms and enhances risk stratification in AML.Cancer cell international · 2026Article
- Emerging Roles of Megakaryocytes in Immune Regulation and Potential Therapeutic Prospects.Cells · 2025Review
- New insights into the generation and function of megakaryocytes in health and disease.Haematologica · 2025Review
- Hypermethylation of DNA impairs megakaryogenesis in delayed platelet recovery after allogeneic hematopoietic stem cell transplantation.Science advances · 2025Article
- Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation.Blood advances · 2025Article
- Transcription factor RUNX1 regulates coagulation factor XIII-A (Research and practice in thrombosis and haemostasis · 2025Article
- RUNX1 isoforms regulate RUNX1 and target genes differentially in platelets-megakaryocytes: association with clinical cardiovascular events.Journal of thrombosis and haemostasis : JTH · 2024Article
- Erythropoietin regulates energy metabolism through EPO-EpoR-RUNX1 axis.Nature communications · 2024Article
- RUNX1 Isoforms Regulate RUNX1 and Target-Genes Differentially in Platelets-Megakaryocytes: Association with Clinical Cardiovascular Events.bioRxiv : the preprint server for biology · 2024Article
- RUNX1 C-terminal mutations impair blood cell differentiation by perturbing specific enhancer-promoter networks.Blood advances · 2024Article
- Altered platelet-megakaryocyte endocytosis and trafficking of albumin and fibrinogen in RUNX1 haplodeficiency.Blood advances · 2024Article
- Article
- Article
- Transcription factors in megakaryocytes and platelets.Frontiers in immunology · 2023Review
- The Analysis of the Human Megakaryocyte and Platelet Coding Transcriptome in Healthy and Diseased Subjects.International journal of molecular sciences · 2022Review
- Article
- Hemostatic phenotypes and genetic disorders.Research and practice in thrombosis and haemostasis · 2021Article
- Helios represses megakaryocyte priming in hematopoietic stem and progenitor cells.The Journal of experimental medicine · 2021Article
- Megakaryopoiesis and Platelet Biology: Roles of Transcription Factors and Emerging Clinical Implications.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with familial platelet disorder with a predisposition to myeloid malignancy (FPDMM) harbor germline monoallelic mutations in a key hematopoietic transcription factor, RUNX-1. Previous studies of FPDMM have focused on megakaryocyte (Mk) differentiation and platelet production and signaling. However, the effects of RUNX-1 haploinsufficiency on hematopoietic progenitor cells (HPCs) and subsequent megakaryopoiesis remains incomplete. We studied induced pluripotent stem cell (iPSC)-derived HPCs (iHPCs) and Mks (iMks) from both patient-derived lines and a wild-type (WT) line modified to be RUNX-1 haploinsufficient (RUNX-1+/-), each compared with their isogenic WT control. All RUNX-1+/- lines showed decreased iMk yield and depletion of an Mk-biased iHPC subpopulation. To investigate global and local gene expression changes underlying this iHPC shift, single-cell RNA sequencing was performed on sorted FPDMM and control iHPCs. We defined several cell subpopulations in the Mk-biased iHPCs. Analyses of gene sets upregulated in FPDMM iHPCs indicated enrichment for response to stress, regulation of signal transduction, and immune signaling-related gene sets. Immunoblot analyses in FPDMM iMks were consistent with these findings, but also identified augmented baseline c-Jun N-terminal kinase (JNK) phosphorylation, known to be activated by transforming growth factor-β1 (TGF-β1) and cellular stressors. These findings were confirmed in adult human CD34+-derived stem and progenitor cells (HSPCs) transduced with lentiviral RUNX1 short hairpin RNA to mimic RUNX-1+/-. In both iHPCs and CD34+-derived HSPCs, targeted inhibitors of JNK and TGF-β1 pathways corrected the megakaryopoietic defect. We propose that such intervention may correct the thrombocytopenia in patients with FPDMM.
Indexed as
Identifiers
What Socratic holds
Registered trials
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 Socratic graph.