In:
Blood, American Society of Hematology, Vol. 112, No. 5 ( 2008-09-01), p. 1942-1950
Abstract:
Ectopic C/EBPα expression in p210BCR/ABL-expressing hematopoietic cells induces granulocytic differentiation, inhibits proliferation, and suppresses leukemogenesis. To assess the underlying mechanisms, C/EBPα targets were identified by microarray analyses. Upon C/EBPα activation, expression of c-Myb and GATA-2 was repressed in 32D-BCR/ABL, K562, and chronic myelogenous leukemia (CML) blast crisis (BC) primary cells but only c-Myb levels decreased slightly in CD34+ normal progenitors. The role of these 2 genes for the effects of C/EBPα was assessed by perturbing their expression in K562 cells. Ectopic c-Myb expression blocked the proliferation inhibition– and differentiation-inducing effects of C/EBPα, whereas c-Myb siRNA treatment enhanced C/EBPα-mediated proliferation inhibition and induced changes in gene expression indicative of monocytic differentiation. Ectopic GATA-2 expression suppressed the proliferation inhibitory effect of C/EBPα but blocked in part the effect on differentiation; GATA-2 siRNA treatment had no effects on C/EBPα induction of differentiation but inhibited proliferation of K562 cells, alone or upon C/EBPα activation. In summary, the effects of C/EBPα in p210BCR/ABL-expressing cells depend, in part, on transcriptional repression of c-Myb and GATA-2. Since perturbation of c-Myb and GATA-2 expression has nonidentical consequences for proliferation and differentiation of K562 cells, the effects of C/EBPα appear to involve dif-ferent transcription-regulated targets.
Type of Medium:
Online Resource
ISSN:
0006-4971
,
1528-0020
DOI:
10.1182/blood-2007-09-114975
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2008
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
