C/EBPß promotes BCR-ABL-mediated myeloid expansion and leukemic stem cell exhaustion.
Leukemia
; 27(3): 619-28, 2013 Mar.
Article
em En
| MEDLINE
| ID: mdl-22948537
ABSTRACT
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 ß (C/EBPß), a regulator for 'emergency granulopoiesis,' in the pathogenesis of CP-CML was examined. C/EBPß 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/EBPß, at least in part, through the activation of STAT5. Myeloid differentiation and proliferation induced by BCR-ABL was significantly impaired in C/EBPß-deficient bone marrow cells in vitro. Mice that were transplanted with BCR-ABL-transduced C/EBPß 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/EBPß-deficient cells than in BCR-ABL-transduced WT cells. These results suggest that C/EBPß is involved in BCR-ABL-mediated myeloid expansion. Further elucidation of the molecular mechanisms underlying the C/EBPß-mediated stem cell loss might reveal a novel therapeutic strategy for eradication of CML stem cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Leucemia Mielogênica Crônica BCR-ABL Positiva
/
Proteínas de Fusão bcr-abl
/
Células Mieloides
/
Proteína beta Intensificadora de Ligação a CCAAT
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Leukemia
Assunto da revista:
HEMATOLOGIA
/
NEOPLASIAS
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Japão