| Literature DB >> 18455126 |
Weili Chen1, Ashish R Kumar, Wendy A Hudson, Quanzhi Li, Baolin Wu, Rodney A Staggs, Erik A Lund, Thien N Sam, John H Kersey.
Abstract
The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin(-)Sca1(+)c-kit(+)) stem cells, while committed granulocyte-monocyte progenitors (GMPs) were transformation resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll-AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 upregulated expression of 192 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.Entities:
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Year: 2008 PMID： 18455126 PMCID： PMC2430522 DOI： 10.1016/j.ccr.2008.03.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743