| RRC ID |
77365
|
| 著者 |
Tsuzuki S, Taguchi O, Seto M.
|
| タイトル |
Promotion and maintenance of leukemia by ERG.
|
| ジャーナル |
Blood
|
| Abstract |
The Ets-related gene (ERG) located on human chromosome 21 encodes a transcription factor and is thought to be causally related to Down syndrome-associated acute megakaryocytic leukemia in childhood. In clinical adult leukemia, however, increased expression of ERG is indicative of poor prognosis in T-cell acute lymphoblastic leukemia and cytogenetically normal acute myeloid leukemia, although the involvement of ERG in the development of adult leukemia remains elusive. Here, we show that forced expression of ERG in adult BM cells alters differentiation and induces expansion of T and erythroid cells and increases frequencies of myeloid progenitors in mouse BM transplantation models. The expanded T cells then develop T-cell acute lymphoblastic leukemia after acquisition of mutations in the Notch1 gene. Targeted expression of ERG into B cells also altered differentiation and promoted growth of precursor B cells. Overall, these findings suggest a general role of ERG in promoting growth of adult hematopoietic cells in various lineages. In line with this, shRNA-mediated silencing of ERG expression attenuated growth of human leukemia cell lines of various lineages. Thus, ERG is capable of promoting the development of leukemia and is crucial for its maintenance.
|
| 巻・号 |
117(14)
|
| ページ |
3858-68
|
| 公開日 |
2011-4-7
|
| DOI |
10.1182/blood-2010-11-320515
|
| PII |
S0006-4971(20)45311-X
|
| PMID |
21321361
|
| MeSH |
Animals
Cell Transformation, Neoplastic / genetics*
Disease Progression
Gene Expression Profiling
Gene Expression Regulation, Leukemic
Humans
Leukemia / genetics*
Leukemia / pathology
Mice
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Microarray Analysis
Neoplasm Transplantation
Oncogene Proteins / genetics
Oncogene Proteins / metabolism
Oncogene Proteins / physiology*
Transcription Factors
Transcriptional Regulator ERG
Transplantation, Heterologous
Tumor Cells, Cultured
|
| IF |
17.794
|
| リソース情報 |
| ヒト・動物細胞 |
OP9(RCB1124) |
