| http://purl.uniprot.org/citations/24255920 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24255920 | http://www.w3.org/2000/01/rdf-schema#comment | "ASXL1 is mutated/deleted with high frequencies in multiple forms of myeloid malignancies, and its alterations are associated with poor prognosis. De novo ASXL1 mutations cause Bohring-Opitz syndrome characterized by multiple congenital malformations. We show that Asxl1 deletion in mice led to developmental abnormalities including dwarfism, anophthalmia, and 80% embryonic lethality. Surviving Asxl1(-/-) mice lived for up to 42 days and developed features of myelodysplastic syndrome (MDS), including dysplastic neutrophils and multiple lineage cytopenia. Asxl1(-/-) mice had a reduced hematopoietic stem cell (HSC) pool, and Asxl1(-/-) HSCs exhibited decreased hematopoietic repopulating capacity, with skewed cell differentiation favoring granulocytic lineage. Asxl1(+/-) mice also developed mild MDS-like disease, which could progress to MDS/myeloproliferative neoplasm, demonstrating a haploinsufficient effect of Asxl1 in the pathogenesis of myeloid malignancies. Asxl1 loss led to an increased apoptosis and mitosis in Lineage(-)c-Kit(+) (Lin(-)c-Kit(+)) cells, consistent with human MDS. Furthermore, Asxl1(-/-) Lin(-)c-Kit(+) cells exhibited decreased global levels of H3K27me3 and H3K4me3 and altered expression of genes regulating apoptosis (Bcl2, Bcl2l12, Bcl2l13). Collectively, we report a novel ASXL1 murine model that recapitulates human myeloid malignancies, implying that Asxl1 functions as a tumor suppressor to maintain hematopoietic cell homeostasis. Future work is necessary to clarify the contribution of microenvironment to the hematopoietic phenotypes observed in the constitutional Asxl1(-/-) mice."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.org/dc/terms/identifier | "doi:10.1182/blood-2013-05-500272"xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Chen S."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "He Y."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Jiang L."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Li Z."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Liu Z."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Nguyen L."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Xu M."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Zhou J."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Wang J."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Yang X."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Yuan J."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Rhodes S."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Ni H."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Pan F."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Yang F.C."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Cai C.L."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/author | "Weeks O."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/name | "Blood"xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/pages | "541-553"xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/title | "Loss of Asxl1 leads to myelodysplastic syndrome-like disease in mice."xsd:string |
| http://purl.uniprot.org/citations/24255920 | http://purl.uniprot.org/core/volume | "123"xsd:string |