|
|
Blood, 15 August 2005, Vol. 106, No. 4, pp. 1369-1375.
Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2004-11-4392.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
CBFB-SMMHC is correlated with increased calreticulin expression and suppresses the granulocytic differentiation factor CEBPA in AML with inv(16)
Daniel Helbling,
Beatrice U. Mueller,
Nikolai A. Timchenko,
Julian Schardt,
Myriam Eyer,
David R. Betts,
Martine Jotterand,
Sandrine Meyer-Monard,
Martin F. Fey, and
Thomas Pabst
From the Department of Clinical Research and Department of Medical Oncology, University Hospital, Berne, Switzerland; Department of Medicine, University Hospital, Berne, Switzerland; Department of Pathology and Huffington Center on Aging, Baylor College of Medicine, Houston, TX; Department of Oncology, University Children Hospital, Zurich, Switzerland; Unit of Cancer Cytogenetics, Service of Medical Genetics, University Hospital, Lausanne, Switzerland; and Division of Haematology, University Hospital, Basel, Switzerland.
The pericentric inversion of chromosome 16, inv(16)(p13q22), is associated with acute myeloid leukemia (AML) subtype M4Eo that is characterized by the presence of myelomonocytic blasts and atypical eosinophils. This rearrangement fuses the CBFB and MYH11 genes, with the latter encoding the smooth muscle myosin heavy chain (SMMHC). The myeloid transcription factor CCAAT/enhancer-binding protein  (CEBPA) is crucial for normal granulopoiesis. Alterations of structure and expression of CEBPA have been implicated in particular subtypes of AML. Here, we found that conditional expression of core-binding factor  (CBFB)-SMMHC in U937 cells suppresses CEBPA protein expression and binding activity. However, CEBPA mRNA levels remained unchanged. No differences were detected in CEBPA mRNA levels in patients with inv(16) AML-M4Eo (n = 12) compared to patients with AML with a normal karyotype and M4 subtype (n = 6), whereas CEBPA protein and binding activity were significantly reduced in patients with CBFB-SMMHC. Furthermore, calreticulin, an inhibitor of CEBPA translation, was induced on mRNA and protein level in CBFB-SMMHC patients with AML and after expression of CBFB-SMMHC in the U937-cell system. Inhibition of calreticulin by siRNA restored CEBPA levels. Our results suggest that modulation of CEBPA by calreticulin represents a novel mechanism involved in the differentiation block in CBFB-SMMHC AML. (Blood. 2005;106:1369-1375)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. Pulsoni, S. Iacobelli, M. Bernardi, M. Borgia, A. Camera, N. Cantore, F. Di Raimondo, P. Fazi, F. Ferrara, F. Leoni, et al.
M4 acute myeloid leukemia: the role of eosinophilia and cytogenetics in treatment response and survival. The GIMEMA experience
Haematologica,
July 1, 2008;
93(7):
1025 - 1032.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Hackanson, K. L. Bennett, R. M. Brena, J. Jiang, R. Claus, S.-S. Chen, N. Blagitko-Dorfs, K. Maharry, S. P. Whitman, T. D. Schmittgen, et al.
Epigenetic Modification of CCAAT/Enhancer Binding Protein {alpha} Expression in Acute Myeloid Leukemia
Cancer Res.,
May 1, 2008;
68(9):
3142 - 3151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Hasemann, I. Damgaard, M. B. Schuster, K. Theilgaard-Monch, A. B. Sorensen, A. Mrsic, T. Krugers, B. Ylstra, F. S. Pedersen, C. Nerlov, et al.
Mutation of C/EBP{alpha} predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen
Blood,
April 15, 2008;
111(8):
4309 - 4321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Koschmieder, F. D'Alo, H. Radomska, C. Schoneich, J. S. Chang, M. Konopleva, S. Kobayashi, E. Levantini, N. Suh, A. Di Ruscio, et al.
CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha
Blood,
November 15, 2007;
110(10):
3695 - 3705.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schepers, A. T. J. Wierenga, D. van Gosliga, B. J. L. Eggen, E. Vellenga, and J. J. Schuringa
Reintroduction of C/EBP{alpha} in leukemic CD34+ stem/progenitor cells impairs self-renewal and partially restores myelopoiesis
Blood,
August 15, 2007;
110(4):
1317 - 1325.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Ferrari-Amorotti, K. Keeshan, M. Zattoni, C. Guerzoni, G. Iotti, S. Cattelani, N. J. Donato, and B. Calabretta
Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBP{alpha}
Blood,
August 15, 2006;
108(4):
1353 - 1362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. T. J. Wierenga, H. Schepers, M. A. S. Moore, E. Vellenga, and J. J. Schuringa
STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic stem/progenitor cells involves down-modulation of C/EBP{alpha}
Blood,
June 1, 2006;
107(11):
4326 - 4333.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
