| First Author | Chen W | Year | 2008 |
| Journal | Cancer Cell | Volume | 13 |
| Issue | 5 | Pages | 432-40 |
| PubMed ID | 18455126 | Mgi Jnum | J:134770 |
| Mgi Id | MGI:3789781 | Doi | 10.1016/j.ccr.2008.03.005 |
| Citation | Chen W, et al. (2008) Malignant transformation initiated by Mll-AF9: gene dosage and critical target cells. Cancer Cell 13(5):432-40 |
| abstractText | 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. |
