論文 - 詳細
| RRC ID | 45251 |
|---|---|
| 著者 | Yoshimi A, Toya T, Kawazu M, Ueno T, Tsukamoto A, Iizuka H, Nakagawa M, Nannya Y, Arai S, Harada H, Usuki K, Hayashi Y, Ito E, Kirito K, Nakajima H, Ichikawa M, Mano H, Kurokawa M. |
| タイトル | Recurrent CDC25C mutations drive malignant transformation in FPD/AML. |
| ジャーナル | Nat Commun |
| Abstract |
Familial platelet disorder (FPD) with predisposition to acute myelogenous leukaemia (AML) is characterized by platelet defects with a propensity for the development of haematological malignancies. Its molecular pathogenesis is poorly understood, except for the role of germline RUNX1 mutations. Here we show that CDC25C mutations are frequently found in FPD/AML patients (53%). Mutated CDC25C disrupts the G2/M checkpoint and promotes cell cycle progression even in the presence of DNA damage, suggesting a critical role for CDC25C in malignant transformation in FPD/AML. The predicted hierarchical architecture shows that CDC25C mutations define a founding pre-leukaemic clone, followed by stepwise acquisition of subclonal mutations that contribute to leukaemia progression. In three of seven individuals with CDC25C mutations, GATA2 is the target of subsequent mutation. Thus, CDC25C is a novel gene target identified in haematological malignancies. CDC25C is also useful as a clinical biomarker that predicts progression of FPD/AML in the early stage. |
| 巻・号 | 5 |
| ページ | 4770 |
| 公開日 | 2014-8-27 |
| DOI | 10.1038/ncomms5770 |
| PII | ncomms5770 |
| PMID | 25159113 |
| MeSH | Animals Blood Platelet Disorders / complications Blood Platelet Disorders / genetics* Blood Platelet Disorders / pathology Cell Cycle / genetics Cell Line Core Binding Factor Alpha 2 Subunit / genetics DNA Damage GATA2 Transcription Factor / genetics Genetic Predisposition to Disease High-Throughput Nucleotide Sequencing Humans Leukemia, Myeloid, Acute / genetics* Leukemia, Myeloid, Acute / pathology Mice Mutation* Pedigree Thrombocytopenia / genetics cdc25 Phosphatases / genetics* cdc25 Phosphatases / metabolism |
| IF | 12.121 |
| 引用数 | 46 |
| WOS 分野 | HEMATOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | Ba/F3(RCB0805) |