ArticleNature medicine2015
Minimal PU.1 reduction induces a preleukemic state and promotes development of acute myeloid leukemia.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 128 citations in OpenAlex.
- Review
- Article
- Epigenetic reactivation of the tumor suppressor ZBTB7A by KDM4 inhibition in human acute myeloid leukemia.Science translational medicine · 2026Article
- Systematic functional dissection of germline noncoding risk variants impacting clonal hematopoiesis.bioRxiv : the preprint server for biology · 2026Article
- Beyond anemia: unraveling neutrophil defects and infection susceptibility in β-Thalassemia.Blood research · 2025Review
- One hundred thirty-four germ line PU.1 variants and the agammaglobulinemic patients carrying them.Blood · 2025Article
- CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.Nature communications · 2025Article
- Chromatin structure and 3D architecture define the differential functions of PU.1 regulatory elements in blood cell lineages.Epigenetics & chromatin · 2024Article
- Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.Nature genetics · 2024Article
- Chemical restriction of PU.1 genomic binding sites activates alternate gene networks.Nature genetics · 2024Article
- The roles of ubiquitination in AML.Annals of hematology · 2024Review
- A multi-omics approach for biomarker discovery in neuroblastoma: a network-based framework.NPJ systems biology and applications · 2024Article
- An iron rheostat controls hematopoietic stem cell fate.Cell stem cell · 2024Article
- The ncBAF Complex Regulates Transcription in AML Through H3K27ac Sensing by BRD9.Cancer research communications · 2024Article
- LILRB3 Modulates Acute Myeloid Leukemia Progression and Acts as an Effective Target for CAR T-cell Therapy.Cancer research · 2023Article
- FANCA deficiency promotes leukaemic progression by allowing the emergence of cells carrying oncogenic driver mutations.Oncogene · 2023Article
- DNA selection by the master transcription factor PU.1.Cell reports · 2023Article
- Review
- PU.1 is required to restrain myelopoiesis during chronic inflammatory stress.Frontiers in cell and developmental biology · 2023Article
- Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas.International journal of cancer · 2022Review
24 more citing papers are in PubMed but not listed here.
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 at 2 institutions in 1 country.
Funding
Abstract
Modest transcriptional changes caused by genetic or epigenetic mechanisms are frequent in human cancer. Although loss or near-complete loss of the hematopoietic transcription factor PU.1 induces acute myeloid leukemia (AML) in mice, a similar degree of PU.1 impairment is exceedingly rare in human AML; yet, moderate PU.1 inhibition is common in AML patients. We assessed functional consequences of modest reductions in PU.1 expression on leukemia development in mice harboring DNA lesions resembling those acquired during human stem cell aging. Heterozygous deletion of an enhancer of PU.1, which resulted in a 35% reduction of PU.1 expression, was sufficient to induce myeloid-biased preleukemic stem cells and their subsequent transformation to AML in a DNA mismatch repair-deficient background. AML progression was mediated by inhibition of expression of a PU.1-cooperating transcription factor, Irf8. Notably, we found marked molecular similarities between the disease in these mice and human myelodysplastic syndrome and AML. This study demonstrates that minimal reduction of a key lineage-specific transcription factor, which commonly occurs in human disease, is sufficient to initiate cancer development, and it provides mechanistic insight into the formation and progression of preleukemic stem cells in AML.
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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.