|
|
Blood, 15 August 2007, Vol. 110, No. 4, pp. 1317-1325.
Prepublished online as a Blood First Edition Paper on May 2, 2007; DOI 10.1182/blood-2006-10-052175.
 Previous Article | Next Article 
Submitted October 13, 2006
Accepted April 29, 2007
Re-introduction of C/EBP in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis
Hein Schepers, Albertus T.J. Wierenga, Djoke van Gosliga, Bart J. L. Eggen, Edo Vellenga, and Jan Jacob Schuringa*
Division of Hematology, Department of Medicine, University Medical Center Groningen, Groningen, Netherlands
Department of Developmental Genetics, University of Groningen, Groningen, Netherlands
* Corresponding author; email: j.schuringa{at}int.umcg.nl.
The CCAAT/enhancer binding protein (C/EBP)  transcription factor is indispensable for myeloid differentiation. In various myeloid leukemias, C/EBP is mutated or functionally impaired due to decreased C/EBP expression or phosphorylation. In order to investigate the functional consequences of decreased C/EBP function in AML, we re-introduced C/EBP in primary CD34+ sorted AML cells using a lentiviral approach. Self-renewal and differentiation of primary AML stem cells were studied on long-term MS5-cocultures. Activation of C/EBP immediately led to a growth arrest in all AML cultures (N=7), resulting in severely reduced expansion as compared to control cultures. This growth arrest corresponded with enhanced myeloid differentiation as assessed by FACS analysis for CD14, CD15 and CD11b. Myeloid differentiation was further confirmed by the upregulation of Neutrophil Elastase and G-CSF-Receptor in C/EBP transduced cells. C/EBP-expressing AML CD34+ cells failed to generate 2nd and 3rd leukemic cobblestone areas (L-CAs) in serial replating experiments, while control cultures could be sequentially passaged for over 4 times, indicating that re-introduction of C/EBP impaired the self-renewal capacity of the leukemic CD34+ compartment. Together, our data indicate that low C/EBP levels are necessary to maintain self-renewal and the immature character of AML stem cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells
- Hein Schepers, Djoke van Gosliga, Albertus T. J. Wierenga, Bart J. L. Eggen, Jan Jacob Schuringa, and Edo Vellenga
Blood 2007 110: 2880-2888.
[Abstract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
A. Rizo, S. Olthof, L. Han, E. Vellenga, G. de Haan, and J. J. Schuringa
Repression of BMI1 in normal and leukemic human CD34+ cells impairs self-renewal and induces apoptosis
Blood,
August 20, 2009;
114(8):
1498 - 1505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kandilci and G. C. Grosveld
Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyperproliferation and restores myeloid differentiation
Blood,
August 20, 2009;
114(8):
1596 - 1606.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. T. J. Wierenga, E. Vellenga, and J. J. Schuringa
Maximal STAT5-Induced Proliferation and Self-Renewal at Intermediate STAT5 Activity Levels
Mol. Cell. Biol.,
November 1, 2008;
28(21):
6668 - 6680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schepers, D. van Gosliga, A. T. J. Wierenga, B. J. L. Eggen, J. J. Schuringa, and E. Vellenga
STAT5 is required for long-term maintenance of normal and leukemic human stem/progenitor cells
Blood,
October 15, 2007;
110(8):
2880 - 2888.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
