| RRC ID |
19298
|
| 著者 |
Moriya K, Suzuki M, Watanabe Y, Takahashi T, Aoki Y, Uchiyama T, Kumaki S, Sasahara Y, Minegishi M, Kure S, Tsuchiya S, Sugamura K, Ishii N.
|
| タイトル |
Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice.
|
| ジャーナル |
PLoS One
|
| Abstract |
Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ(-/-) (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia.
|
| 巻・号 |
7(6)
|
| ページ |
e37892
|
| 公開日 |
2012-1-1
|
| DOI |
10.1371/journal.pone.0037892
|
| PII |
PONE-D-12-06454
|
| PMID |
22745659
|
| PMC |
PMC3380045
|
| MeSH |
Animals
Blotting, Southern
Disease Models, Animal
Flow Cytometry
Hematopoietic Stem Cells / cytology
Hematopoietic Stem Cells / metabolism
Humans
Leukemia / genetics
Leukemia / metabolism*
Mice
Myeloid-Lymphoid Leukemia Protein / genetics
Myeloid-Lymphoid Leukemia Protein / metabolism*
Oncogene Proteins, Fusion / genetics
Oncogene Proteins, Fusion / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / genetics
Transcription Factors / metabolism
|
| IF |
2.74
|
| 引用数 |
58
|
|
WOS 分野
|
HEMATOLOGY
|
| リソース情報 |
| 研究用ヒト臍帯血幹細胞 |
臍帯血
研究用ヒト臍帯血幹細胞 |
