Back to Search
Start Over
BCR-ABL suppresses C/EBPα expression through inhibitory action of hnRNP E2.
- Source :
- Nature Genetics; Jan2002, Vol. 30 Issue 1, p48, 11p
- Publication Year :
- 2002
-
Abstract
- The arrest of differentiation is a feature of both chronic myelogenous leukemia cells in myeloid blast crisis and myeloid precursors that ectopically express the p210[sup BCR-ABL] oncoprotein; however, its underlying mechanisms remain poorly understood. Here we show that expression of BCR-ABL in myeloid precursor cells leads to transcriptional suppression of the granulocyte colony-stimulating factor receptor G-CSF-R (encoded by CSF3R), possibly through down-modulation of C/EBPα—the principal regulator of granulocytic differentiation. Expression of C/EBPα protein is barely detectable in primary marrow cells taken from individuals affected with chronic myeloid leukemia in blast crisis. In contrast, CEBPA RNA is clearly present. Ectopic expression of C/EBPα induces granulocytic differentiation of myeloid precursor cells expressing BCR-ABL. Expression of C/EBPα is suppressed at the translational level by interaction of the poly(rC)-binding protein hnRNP E2 with CEBPA mRNA, and ectopic expression of hnRNP E2 in myeloid precursor cells down-regulates both C/EBPα and G-CSF-R and leads to rapid cell death on treatment with G-CSF (encoded by CSF3). Our results indicate that BCR-ABL regulates the expression of C/EBPα by inducing hnRNP E2—which inhibits the translation of CEBPA mRNA. [ABSTRACT FROM AUTHOR]
- Subjects :
- MYELOID leukemia
GRANULOCYTE-macrophage colony-stimulating factor
Subjects
Details
- Language :
- English
- ISSN :
- 10614036
- Volume :
- 30
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Genetics
- Publication Type :
- Academic Journal
- Accession number :
- 8781659
- Full Text :
- https://doi.org/10.1038/ng791