ArticleJCI insight2021
p300 suppresses the transition of myelodysplastic syndromes to acute myeloid leukemia.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Rapidly progressing after umbilical cord blood transplantation in a boy with acute myeloid leukemia with KAT6A::EP300 fusion transcript.Annals of hematology · 2025Article
- Tracking-seq reveals the heterogeneity of off-target effects in CRISPR-Cas9-mediated genome editing.Nature biotechnology · 2025Article
- Baf155 controls hematopoietic differentiation and regeneration through chromatin priming.Cell reports · 2024Article
- Function of serine/arginine-rich splicing factors in hematopoiesis and hematopoietic malignancies.Cancer cell international · 2024Review
- RSL3 enhances ROS-mediated cell apoptosis of myelodysplastic syndrome cells through MYB/Bcl-2 signaling pathway.Cell death & disease · 2024Article
- Review
- The SWI/SNF chromatin-remodeling subunit DPF2 facilitates NRF2-dependent antiinflammatory and antioxidant gene expression.The Journal of clinical investigation · 2023Article
- Secondary Acute Myeloid Leukemia in Myelodysplastic Syndrome Patients Aged Over 60 Years.Cureus · 2023Review
- The Role of CREBBP/EP300 and Its Therapeutic Implications in Hematological Malignancies.Cancers · 2023Review
- Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300.Haematologica · 2023Article
- KATs off: Biomedical insights from lysine acetyltransferase inhibitors.Current opinion in chemical biology · 2023Review
- Targeted Epigenetic Interventions in Cancer with an Emphasis on Pediatric Malignancies.Biomolecules · 2022Review
- SNCA genetic lowering reveals differential cognitive function of alpha-synuclein dependent on sex.Acta neuropathologica communications · 2022Article
- A Phenogenetic Axis that Modulates Clinical Manifestation and Predicts Treatment Outcome in Primary Myeloid Neoplasms.Cancer research communications · 2022Article
- Advances in molecular characterization of myeloid proliferations associated with Down syndrome.Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Myelodysplastic syndromes (MDS) are hematopoietic stem and progenitor cell (HSPC) malignancies characterized by ineffective hematopoiesis and an increased risk of leukemia transformation. Epigenetic regulators are recurrently mutated in MDS, directly implicating epigenetic dysregulation in MDS pathogenesis. Here, we identified a tumor suppressor role of the acetyltransferase p300 in clinically relevant MDS models driven by mutations in the epigenetic regulators TET2, ASXL1, and SRSF2. The loss of p300 enhanced the proliferation and self-renewal capacity of Tet2-deficient HSPCs, resulting in an increased HSPC pool and leukemogenicity in primary and transplantation mouse models. Mechanistically, the loss of p300 in Tet2-deficient HSPCs altered enhancer accessibility and the expression of genes associated with differentiation, proliferation, and leukemia development. Particularly, p300 loss led to an increased expression of Myb, and the depletion of Myb attenuated the proliferation of HSPCs and improved the survival of leukemia-bearing mice. Additionally, we show that chemical inhibition of p300 acetyltransferase activity phenocopied Ep300 deletion in Tet2-deficient HSPCs, whereas activation of p300 activity with a small molecule impaired the self-renewal and leukemogenicity of Tet2-deficient cells. This suggests a potential therapeutic application of p300 activators in the treatment of MDS with TET2 inactivating mutations.
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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.