論文 - 詳細
| RRC ID | 11033 |
|---|---|
| 著者 | Kawagoe H, Grosveld GC. |
| タイトル | Conditional MN1-TEL knock-in mice develop acute myeloid leukemia in conjunction with overexpression of HOXA9. |
| ジャーナル | Blood |
| Abstract |
The chromosomal translocation t(12; 22)(p13;q11) in human myeloid leukemia generates an MN1-TEL (meningioma 1-translocation-ETS-leukemia) fusion oncoprotein. This protein consists of N-terminal MN1 sequences, a transcriptional coactivator fused to C-terminal TEL sequences, an ETS (E26 transformation-specific) transcription factor. Enforced expression of MN1-TEL in multipotent hematopoietic progenitors in knock-in mice perturbed growth and differentiation of myeloid as well as lymphoid cells. Depending on obligatory secondary mutations, these mice developed T-cell lympholeukemia. Here we addressed the role of MN1-TEL in myeloid leukemogenesis using the same mouse model. Expression of MN1-TEL enhanced the growth of myeloid progenitors in an interleukin 3/stem cell factor (IL-3/SCF)-dependent manner in vitro whereas 10% of MN1-TEL-expressing mice developed altered myelopoiesis with severe anemia after long latency. Coexpression of MN1-TEL and IL-3, but not SCF, rapidly caused a fatal myeloproliferative disease rather than acute myeloid leukemia (AML). Because MN1-TEL+ AML patient cells overexpress HOXA9 (homeobox A9), we tested the effect of coexpression of MN1-TEL and HOXA9 in mice and found that 90% of MN1-TEL+/HOXA9+ mice developed AML much more rapidly than control HOXA9+ mice. Thus, the leukemogenic effect of MN1-TEL in our knock-in mice is pleiotropic, and the type of secondary mutation determines disease outcome. |
| 巻・号 | 106(13) |
| ページ | 4269-77 |
| 公開日 | 2005-12-15 |
| DOI | 10.1182/blood-2005-04-1679 |
| PII | S0006-4971(20)67743-6 |
| PMID | 16105979 |
| PMC | PMC1895240 |
| MeSH | Animals Cell Proliferation Cells, Cultured Cytokines / pharmacology Gene Expression Regulation, Neoplastic Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Humans Leukemia, Myeloid, Acute / genetics Leukemia, Myeloid, Acute / metabolism* Leukemia, Myeloid, Acute / pathology* Mice Mice, Transgenic Myeloid Progenitor Cells / cytology Myeloid Progenitor Cells / drug effects Myeloid Progenitor Cells / metabolism Oncogene Proteins / genetics Oncogene Proteins / metabolism* Proto-Oncogene Proteins c-ets / genetics Proto-Oncogene Proteins c-ets / metabolism* Proto-Oncogene Proteins c-myc / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism* Trans-Activators Transgenes / genetics Tumor Suppressor Proteins |
| IF | 17.794 |
| 引用数 | 33 |
| 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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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 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 | |
| 遺伝子材料 | pCAmKL (RDB1528) pCAmIL3 (RDB1506) |