論文 - 詳細
| RRC ID | 1527 |
|---|---|
| 著者 | Maeda T, Yagasaki F, Ishikawa M, Takahashi N, Bessho M. |
| タイトル | Transforming property of TEL-FGFR3 mediated through PI3-K in a T-cell lymphoma that subsequently progressed to AML. |
| ジャーナル | Blood |
| Abstract |
We previously reported a novel fusion between TEL and FGFR3 in a patient with peripheral T-cell lymphoma with t(4; 12)(p16;p13). Disease in this patient subsequently progressed to acute myelogenous leukemia (AML) with the same translocation. Sequence analysis of TEL-FGFR3 fusion transcripts suggested that these diseases originated from the same multipotent stem cell. To determine the transforming property of TEL-FGFR3, we established transfectants of this chimeric fusion gene and investigated the major signal pathways of TEL-FGFR3-induced transformation using various signal transduction inhibitors including SU5402 (fibroblast growth factor tyrosine kinase [FGFR TK] inhibitor). Our results indicated that (1) the expression of TEL-FGFR3 but not DeltaHLH-TEL-FGFR3 resulted in efficient focus formation in NIH/3T3 cells and conferred interleukin 3 independence to Ba/F3 cells by a constitutive tyrosine kinase activity probably through oligomerization by the HLH domain of TEL; (2) although effector proteins including classical mitogen-activated protein kinase (MAPK), p38 MAPK, phosphatidylinositol 3-kinase (PI3-K), mammalian target or rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT-3) and STAT-5 were activated in TEL-FGFR3 transformants, the growth of the transformants was inhibited by SU5402 (concentration that inhibits 50% [IC5)]=5 microM) and the PI3-K inhibitor, LY294002 (IC5)=10 microM) and wortmannin (IC50=5 microM), but not by U0126, SB203580, or rapamycin; and (3) injection of TEL-FGFR3 transformants induced lethal leukemia into syngeneic mice. Taken together, the leukemogenic potential of TEL-FGFR3 may be mediated in part through PI3-K. |
| 巻・号 | 105(5) |
| ページ | 2115-23 |
| 公開日 | 2005-3-1 |
| DOI | 10.1182/blood-2003-12-4290 |
| PII | S0006-4971(20)45825-2 |
| PMID | 15514005 |
| MeSH | Acute Disease Animals Cell Line Cell Proliferation Cell Transformation, Neoplastic* Disease Progression Female Humans Leukemia, Myeloid / etiology* Lymphoma, T-Cell / pathology* Mice Middle Aged Oncogene Proteins, Fusion / genetics Oncogene Proteins, Fusion / physiology* Phosphatidylinositol 3-Kinases / metabolism* Receptor, Fibroblast Growth Factor, Type 3 Signal Transduction Transfection |
| IF | 17.794 |
| 引用数 | 24 |
| 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 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 43 |
| 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 | Ba/F3(RCB0805) |