ArticleHaematologica2025
FLI1 and GATA1 govern
Article in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Heterozygous nonsenseResearch and practice in thrombosis and haemostasis · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Germline variants of FLI1, essential for megakaryopoiesis, are linked to bleeding disorders, platelet aggregation defects and mild thrombocytopenia. However, the mechanisms behind these abnormalities remain unclear. This study aims to elucidate the impact of FLI1 variants on human megakaryocytes and platelets. We focused on four FLI1 variants, two of which are novel: p.G307R and p.R340C. We assessed the impact of FLI1 variants on megakaryopoiesis using single-cell RNA sequencing, and defects were confirmed in patients' platelets and cell lines. Results showed variants p.R337Q, p.K345E and p.R340C exhibited faulty nuclear localization and defective transcriptional activity in vitro and variants p.K345E and p.G307R affected protein stability. A total of 626 genes were differentially expressed in patient megakaryocytes, including genes associated with the platelet activation pathway. TLN1 was among the most down-regulated genes, with an 88% reduction in talin-1 protein levels in FLI1 patients' platelets. Analysis of chromatin immunoprecipitation sequencing data revealed FLI1-binding regions in the TLN1 gene. Luciferase reporter gene assays revealed the functional role of an intronic binding region in cooperation with GATA1. FLI1 variants were linked to reduced cooperative transcriptional activity. These findings reveal novel mechanisms underlying the pathogenicity of FLI1 variants. Defective cooperation between FLI1 variants and GATA1 may play a role in talin-1 deficiency in FLI1 patients' platelets, thus contributing to platelet dysfunction. Moreover, talin-1 could serve as a biomarker for classifying the pathogenicity of FLI1 variants.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.