ArticleBlood2014
The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
- Review
- Runx-CBFβ regulates the development of tolerogenic Thetis cells.Nature immunology · 2026Article
- Identification of PANoptosis-based signature for predicting the prognosis and immunotherapy response in AML.Heliyon · 2024Article
- Stem cell-like reprogramming is required for leukemia-initiating activity in B-ALL.The Journal of experimental medicine · 2024Article
- PU.1-c-Jun interaction is crucial for PU.1 function in myeloid development.Communications biology · 2022Article
- Article
- Myeloid lncRNA LOUP mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML.Blood · 2021Article
- MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism.Cancer cell · 2021Article
- Cooperating, congenital neutropenia-associated Csf3r and Runx1 mutations activate pro-inflammatory signaling and inhibit myeloid differentiation of mouse HSPCs.Annals of hematology · 2020Article
- Dysregulation of NIPBL leads to impaired RUNX1 expression and haematopoietic defects.Journal of cellular and molecular medicine · 2020Article
- Article
- RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.International journal of molecular sciences · 2019Review
- Pharmacological inhibition of the transcription factor PU.1 in leukemia.The Journal of clinical investigation · 2017Article
- Senescence is a Spi1-induced anti-proliferative mechanism in primary hematopoietic cells.Haematologica · 2017Article
- Automatic identification of informative regions with epigenomic changes associated to hematopoiesis.Nucleic acids research · 2017Article
- Tumor suppressor BLU promotes TRAIL-induced apoptosis by downregulating NF-κB signaling in nasopharyngeal carcinoma.Oncotarget · 2017Article
- Role of RUNX1 in hematological malignancies.Blood · 2017Review
- RUNX1 induces DNA replication independent active DNA demethylation at SPI1 regulatory regions.BMC molecular biology · 2017Article
- A novel PAD4/SOX4/PU.1 signaling pathway is involved in the committed differentiation of acute promyelocytic leukemia cells into granulocytic cells.Oncotarget · 2016Article
- Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.Leukemia · 2016Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 5 countries.
Funding
Abstract
Runx transcription factors contribute to hematopoiesis and are frequently implicated in hematologic malignancies. All three Runx isoforms are expressed at the earliest stages of hematopoiesis; however, their function in hematopoietic stem cells (HSCs) is not fully elucidated. Here, we show that Runx factors are essential in HSCs by driving the expression of the hematopoietic transcription factor PU.1. Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the -14kb enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. Consequently, decreased PU.1 levels resulted in diminished long-term HSC function through HSC exhaustion, which could be rescued by reintroducing a PU.1 transgene. Similarly, in a mouse model of AML/ETO9a leukemia, disrupting the Runx binding sites resulted in decreased PU.1 levels. Leukemia onset was delayed, and limiting dilution transplantation experiments demonstrated functional loss of leukemia-initiating cells. This is surprising, because low PU.1 levels have been considered a hallmark of AML/ETO leukemia, as indicated in mouse models and as shown here in samples from leukemic patients. Our data demonstrate that Runx-dependent PU.1 chromatin interaction and transcription of PU.1 are essential for both normal and leukemia stem cells.
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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.