| First Author | Hayashi Y | Year | 2013 |
| Journal | Leukemia | Volume | 27 |
| Issue | 3 | Pages | 619-28 |
| PubMed ID | 22948537 | Mgi Jnum | J:196803 |
| Mgi Id | MGI:5489964 | Doi | 10.1038/leu.2012.258 |
| Citation | Hayashi Y, et al. (2013) C/EBPbeta promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion. Leukemia 27(3):619-28 |
| abstractText | The BCR-ABL fusion oncoprotein accelerates differentiation and proliferation of myeloid cells during the chronic phase of chronic myeloid leukemia (CP-CML). Here, the role of CCAAT/enhancer binding protein beta (C/EBPbeta), a regulator for 'emergency granulopoiesis,' in the pathogenesis of CP-CML was examined. C/EBPbeta expression was upregulated in Lineage(-) CD34(+) CD38(-) hematopoietic stem cells (HSCs) and myeloid progenitors isolated from bone marrow of patients with CP-CML. In EML cells, a mouse HSC line, BCR-ABL upregulated C/EBPbeta, at least in part, through the activation of STAT5. Myeloid differentiation and proliferation induced by BCR-ABL was significantly impaired in C/EBPbeta-deficient bone marrow cells in vitro. Mice that were transplanted with BCR-ABL-transduced C/EBPbeta knockout bone marrow cells survived longer than mice that received BCR-ABL-transduced wild-type (WT) bone marrow cells. Significantly higher levels of leukemic stem cells were maintained in BCR-ABL-transduced C/EBPbeta-deficient cells than in BCR-ABL-transduced WT cells. These results suggest that C/EBPbeta is involved in BCR-ABL-mediated myeloid expansion. Further elucidation of the molecular mechanisms underlying the C/EBPbeta-mediated stem cell loss might reveal a novel therapeutic strategy for eradication of CML stem cells. |
