ArticleBlood2011
Crebbp haploinsufficiency in mice alters the bone marrow microenvironment, leading to loss of stem cells and excessive myelopoiesis.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Article
- Functional analysis of a novel pathogenic variant in CREBBP associated with bone development.Pediatric research · 2024Article
- The Role of CREBBP/EP300 and Its Therapeutic Implications in Hematological Malignancies.Cancers · 2023Review
- Hematotoxic Effect of Respiratory Exposure to PHMG-p and Its Integrated Genetic Analysis.Toxics · 2022Article
- Pathogenic Mechanisms in Acute Myeloid Leukemia.Current treatment options in oncology · 2022Review
- Dynamic changes in O-GlcNAcylation regulate osteoclast differentiation and bone loss via nucleoporin 153.Bone research · 2022Article
- The role of Trithorax family regulating osteogenic and Chondrogenic differentiation in mesenchymal stem cells.Cell proliferation · 2022Review
- Etoposide, an anticancer drug involved in therapy-related secondary leukemia: Enzymes at play.Translational oncology · 2021Review
- Bone marrow niches in myelodysplastic syndromes.Journal of cancer metastasis and treatment · 2021Article
- Article
- Bone marrow niches in haematological malignancies.Nature reviews. Cancer · 2020Review
- Article
- Inhibition of WNT signaling in the bone marrow niche prevents the development of MDS in theBlood · 2017Article
- Fbxw7 haploinsufficiency loses its protection against DNA damage and accelerates MNU-induced gastric carcinogenesis.Oncotarget · 2017Article
- A myeloid tumor suppressor role forThe Journal of experimental medicine · 2017Article
- The hematopoietic stem-cell niche in health and leukemia.Cellular and molecular life sciences : CMLS · 2017Review
- Review
- Context Matters: Distinct Disease Outcomes as a Result of Crebbp Hemizygosity in Different Mouse Bone Marrow Compartments.PloS one · 2016Article
- Revisiting the case for genetically engineered mouse models in human myelodysplastic syndrome research.Blood · 2015Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
CREB-binding protein (CREBBP) is important for the cell-autonomous regulation of hematopoiesis, including the stem cell compartment. In the present study, we show that CREBBP plays an equally pivotal role in microenvironment-mediated regulation of hematopoiesis. We found that the BM microenvironment of Crebbp(+/-) mice was unable to properly maintain the immature stem cell and progenitor cell pools. Instead, it stimulates myeloid differentiation, which progresses into a myeloproliferation phenotype. Alterations in the BM microenvironment resulting from haploinsufficiency of Crebbp included a marked decrease in trabecular bone that was predominantly caused by increased osteoclastogenesis. Although CFU-fibroblast (CFU-F) and total osteoblast numbers were decreased, the bone formation rate was similar to that found in wild-type mice. At the molecular level, we found that the known hematopoietic modulators matrix metallopeptidase-9 (MMP9) and kit ligand (KITL) were decreased with heterozygous levels of Crebbp. Lastly, potentially important regulatory proteins, endothelial cell adhesion molecule 1 (ESAM1) and cadherin 5 (CDH5), were increased on Crebbp(+/-) endothelial cells. Our findings reveal that a full dose of Crebbp is essential in the BM microenvironment to maintain proper hematopoiesis and to prevent excessive myeloproliferation.
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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.