| First Author | Bereshchenko O | Year | 2009 |
| Journal | Cancer Cell | Volume | 16 |
| Issue | 5 | Pages | 390-400 |
| PubMed ID | 19878871 | Mgi Jnum | J:153947 |
| Mgi Id | MGI:4366640 | Doi | 10.1016/j.ccr.2009.09.036 |
| Citation | Bereshchenko O, et al. (2009) Hematopoietic stem cell expansion precedes the generation of committed myeloid leukemia-initiating cells in C/EBPalpha mutant AML. Cancer Cell 16(5):390-400 |
| abstractText | We here use knockin mutagenesis in the mouse to model the spectrum of acquired CEBPA mutations in human acute myeloid leukemia. We find that C-terminal C/EBPalpha mutations increase the proliferation of long-term hematopoietic stem cells (LT-HSCs) in a cell-intrinsic manner and override normal HSC homeostasis, leading to expansion of premalignant HSCs. However, such mutations impair myeloid programming of HSCs and block myeloid lineage commitment when homozygous. In contrast, N-terminal C/EBPalpha mutations are silent with regards to HSC expansion, but allow the formation of committed myeloid progenitors, the templates for leukemia-initiating cells. The combination of N- and C-terminal C/EBPalpha mutations incorporates both features, accelerating disease development and explaining the clinical prevalence of this configuration of CEBPA mutations. |
