RRC ID 19298
Author 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.
Title Development of a multi-step leukemogenesis model of MLL-rearranged leukemia using humanized mice.
Journal 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.
Volume 7(6)
Pages e37892
Published 2012
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 2.776
Times Cited 13
Cord blood stem cells for research 臍帯血 研究用ヒト臍帯血幹細胞