論文 - 詳細
| RRC ID | 67526 |
|---|---|
| 著者 | Saliba J, Saint-Martin C, Di Stefano A, Lenglet G, Marty C, Keren B, Pasquier F, Valle VD, Secardin L, Leroy G, Mahfoudhi E, Grosjean S, Droin N, Diop M, Dessen P, Charrier S, Palazzo A, Merlevede J, Meniane JC, Delaunay-Darivon C, Fuseau P, Isnard F, Casadevall N, Solary E, Debili N, Bernard OA, Raslova H, Najman A, Vainchenker W, Bellanné-Chantelot C, Plo I. |
| タイトル | Germline duplication of ATG2B and GSKIP predisposes to familial myeloid malignancies. |
| ジャーナル | Nat Genet |
| Abstract |
No major predisposition gene for familial myeloproliferative neoplasms (MPN) has been identified. Here we demonstrate that the autosomal dominant transmission of a 700-kb duplication in four genetically related families predisposes to myeloid malignancies, including MPN, frequently progressing to leukemia. Using induced pluripotent stem cells and primary cells, we demonstrate that overexpression of ATG2B and GSKIP enhances hematopoietic progenitor differentiation, including of megakaryocytes, by increasing progenitor sensitivity to thrombopoietin (TPO). ATG2B and GSKIP cooperate with acquired JAK2, MPL and CALR mutations during MPN development. Thus, the germline duplication may change the fitness of cells harboring signaling pathway mutations and increases the probability of disease development. |
| 巻・号 | 47(10) |
| ページ | 1131-40 |
| 公開日 | 2015-10-1 |
| DOI | 10.1038/ng.3380 |
| PII | ng.3380 |
| PMID | 26280900 |
| MeSH | Adolescent Adult Aged Autophagy-Related Proteins Child Chromosomes, Human, Pair 14 Female Gene Duplication* Genetic Predisposition to Disease* Germ Cells* Humans Induced Pluripotent Stem Cells / cytology Infant Leukemia, Myeloid, Acute / genetics* Male Myelodysplastic Syndromes / genetics* Pedigree Phenotype Repressor Proteins / genetics* Vesicular Transport Proteins / genetics* Young Adult |
| IF | 27.605 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | OP9(RCB1124) |