| http://purl.uniprot.org/citations/25659036 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25659036 | http://www.w3.org/2000/01/rdf-schema#comment | "T-cell acute lymphoblastic leukemia (T-ALL) is a cancer of immature T cells that exhibits heterogeneity of oncogenic lesions, providing an obstacle for development of more effective and less toxic therapies. Inherited deficiency of ATM, a regulator of the cellular DNA damage response, predisposes young humans and mice to T-ALLs with clonal chromosome translocations. While acquired ATM mutation or deletion occurs in pediatric T-ALLs, the role of somatic ATM alterations in T-ALL pathogenesis remains unknown. We demonstrate here that somatic Atm inactivation in haematopoietic cells starting as these cells differentiate in utero predisposes mice to T-ALL at similar young ages and harboring analogous translocations as germline Atm-deficient mice. However, some T-ALLs from haematopoietic cell specific deletion of Atm were of more mature thymocytes, revealing that the developmental timing and celluar origin of Atm inactivation influences the phenotype of ATM-deficient T-ALLs. Although it has been hypothesized that ATM suppresses cancer by preventing deletion and inactivation of TP53, we find that Atm inhibits T-ALL independent of Tp53 deletion. Finally, we demonstrate that the Cyclin D3 protein that drives immature T cell proliferation is essential for transformation of Atm-deficient thymocytes. Our study establishes a pre-clinical model for pediatric T-ALLs with acquired ATM inactivation and identifies the cell cycle machinery as a therapeutic target for this aggressive childhood T-ALL subtype."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.org/dc/terms/identifier | "doi:10.4161/15384101.2014.988020"xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/author | "Bassing C.H."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/author | "Ehrlich L.A."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/author | "DeMicco A."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/author | "Yang-Iott K."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/name | "Cell Cycle"xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/pages | "388-398"xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/title | "Somatic inactivation of ATM in hematopoietic cells predisposes mice to cyclin D3 dependent T cell acute lymphoblastic leukemia."xsd:string |
| http://purl.uniprot.org/citations/25659036 | http://purl.uniprot.org/core/volume | "14"xsd:string |
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