期刊
CANCER SCIENCE
卷 106, 期 3, 页码 227-236出版社
WILEY
DOI: 10.1111/cas.12593
关键词
Acute myeloid leukemia; CSF-1R; mixed lineage leukemia; Spi-1; stem cells
类别
资金
- Ministry of Health, Labor and Welfare, Japan
- National Cancer Center Research and Development Fund, Japan
- US National Institutes of Health [HL112719, CA32551, 5P30-CA13330]
Acute myeloid leukemia is a clonal malignant disorder derived from a small number of leukemic stem cells (LSCs). Rearrangements of the mixed lineage leukemia (MLL) gene are found in acute myeloid leukemia associated with poor prognosis. The upregulation of Hox genes is critical for LSC induction and maintenance, but is unlikely to support malignancy and the high LSC frequency observed in MLL leukemias. The present study shows that MLL fusion proteins interact with the transcription factor PU.1 to activate the transcription of CSF-1R, which is critical for LSC activity. Acute myeloid leukemia is cured by either deletion of PU.1 or ablation of cells expressing CSF-1R. Kinase inhibitors specific for CSF-1R prolong survival time. These findings indicate that PU.1-mediated upregulation of CSF-1R is a critical effector of MLL leukemogenesis.
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