A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder

Almazni, Ibrahim; Chudakou, Pavel; Dawson-Meadows, Alison; Downes, Kate; Freson, Kathleen; Mason, Joanne; Page, Paula; Reay, Kim; Myers, Bethan; Morgan, Neil V.

doi:10.1080/09537104.2021.1887470

Cited by 4 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RUNX1 (Runt-related transcription factor 1) is one of the RUNX transcription factor families. 7 It has been reported to be a key regulator in the TGF-β signalling pathway, preventing progression of hepatocellular carcinoma. 8 In view of this, previous studies have suggested that RUNX1 may play an important role in regulating organ fibrosis -presumably via interacting with the intracellular TGF-β/Smad signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Guo

Liu

Zhao

et al. 2023

Int J Experimental Path

View full text Add to dashboard Cite

Liver fibrosis is caused by chronic liver injury. There are limited treatments for it, and the pathogenesis is unclear. Therefore, there is an urgent need to explore the pathogenesis of liver fibrosis, and to try to identify new potential therapeutic targets. For this study we used the carbon tetrachloride abdominal injection induced liver fibrosis animal model in mice. Primary hepatic stellate cell isolation was performed by a density‐gradient separation method, and this was followed by immunofluorescence stain analyses. Signal pathway analysis was performed by dual‐luciferase reporter assay and western blotting. Our results showed that RUNX1 was upregulated in cirrhotic liver tissues compared with normal liver tissues. Besides, overexpression of RUNX1 caused more severe liver fibrosis lesions than control group under CCl4‐induced conditions. Moreover, α‐SMA expression in the RUNX1 overexpression group was significantly higher than in the control group. Interestingly, we found that RUNX1 could promote the activation of TGF‐β/Smads in a dual‐luciferase reporter assay. Thus we demonstrated that RUNX1 could be considered as a new regulator of hepatic fibrosis by activating TGF‐β/Smads signalling. Based on this, we concluded that RUNX1 may be developed as a new therapeutic target in the treatment of liver fibrosis in the future. In addition, this study also provides a new insight about the aetiology of liver fibrosis.

show abstract

Section: Introductionmentioning

confidence: 99%

“…RUNX1 (Runt‐related transcription factor 1) is one of the RUNX transcription factor families 7 . It has been reported to be a key regulator in the TGF‐β signalling pathway, preventing progression of hepatocellular carcinoma 8 .…”

Section: Introductionmentioning

confidence: 99%

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Guo

Liu

Zhao

et al. 2023

Int J Experimental Path

View full text Add to dashboard Cite

show abstract

Acute myeloid leukemia in a child with familial platelet disorder and a cryptic runx1 intragenic deletion

Dodson

Kurtz

Marcogliese

et al. 2022

Pediatric Hematology and Oncology

View full text Add to dashboard Cite

Germline and somatic drivers in inherited hematologic malignancies

Zoller,

Trajanova,

Feurstein

2023

Front. Oncol.

View full text Add to dashboard Cite

Inherited hematologic malignancies are linked to a heterogenous group of genes, knowledge of which is rapidly expanding using panel-based next-generation sequencing (NGS) or whole-exome/whole-genome sequencing. Importantly, the penetrance for these syndromes is incomplete, and disease development, progression or transformation has critical clinical implications. With the earlier detection of healthy carriers and sequential monitoring of these patients, clonal hematopoiesis and somatic driver variants become significant factors in determining disease transformation/progression and timing of (preemptive) hematopoietic stem cell transplant in these patients. In this review, we shed light on the detection of probable germline predisposition alleles based on diagnostic/prognostic ‘somatic’ NGS panels. A multi-tier approach including variant allele frequency, bi-allelic inactivation, persistence of a variant upon clinical remission and mutational burden can indicate variants with high pre-test probability. We also discuss the shared underlying biology and frequency of germline and somatic variants affecting the same gene, specifically focusing on variants in DDX41, ETV6, GATA2 and RUNX1. Germline variants in these genes are associated with a (specific) pattern or over-/underrepresentation of somatic molecular or cytogenetic alterations that may help identify the underlying germline syndrome and predict the course of disease in these individuals. This review is based on the current knowledge about somatic drivers in these four syndromes by integrating data from all published patients, thereby providing clinicians with valuable and concise information.

show abstract

A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder

Cited by 4 publications

References 17 publications

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

RUNX1 promotes liver fibrosis progression through regulating TGF‐β signalling

Acute myeloid leukemia in a child with familial platelet disorder and a cryptic runx1 intragenic deletion

Germline and somatic drivers in inherited hematologic malignancies

Contact Info

Product

Resources

About