|
|
Blood, 15 April 2005, Vol. 105, No. 8, pp. 3303-3311.
Prepublished online as a Blood First Edition Paper on December 30, 2004; DOI 10.1182/blood-2004-02-0749.
 Previous Article | Table of Contents | Next Article 
NEOPLASIA
Identification of mcl-1 as a BCR/ABL-dependent target in chronic myeloid leukemia (CML): evidence for cooperative antileukemic effects of imatinib and mcl-1 antisense oligonucleotides
Karl J. Aichberger,
Matthias Mayerhofer,
Maria-Theresa Krauth,
Hans Skvara,
Stefan Florian,
Karoline Sonneck,
Cahit Akgul,
Sophia Derdak,
Winfried F. Pickl,
Volker Wacheck,
Edgar Selzer,
Brett P. Monia,
Richard Moriggl,
Peter Valent, and
Christian Sillaber
From the Department of Internal Medicine I, Division of Hematology and Hemostaseology, Department of Radiation Therapy, Institute of Immunology, Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria; Department of Chemistry, Canakkale Onsekiz Mart University, Canakkale, Turkey; ISIS Pharmaceuticals Inc, Carlsbad, CA; and Institute of Molecular Pathology (IMP), Vienna, Austria.
Antiapoptotic members of the bcl-2 family have recently been implicated in the pathogenesis of chronic myeloid leukemia (CML), a hematopoietic neoplasm associated with the BCR/ABL oncogene. We have examined expression of MCL-1 in primary CML cells and BCR/ABL-transformed cell lines. Independent of the phase of disease, isolated primary CML cells expressed myeloid cell leukemia-1 (mcl-1) mRNA and the MCL-1 protein in a constitutive manner. The BCR/ABL inhibitor imatinib (=STI571) decreased the expression of MCL-1 in these cells. Correspondingly, BCR/ABL enhanced mcl-1 promoter activity, mcl-1 mRNA expression, and the MCL-1 protein in Ba/F3 cells. BCR/ABL-dependent expression of MCL-1 in Ba/F3 cells was counteracted by the mitogen-activated protein-kinase/extracellular signal-regulated kinase (MEK) inhibitor, PD98059, but not by the phosphoinositide 3-kinase inhibitor, LY294002. Identical results were obtained for constitutive expression of MCL-1 in primary CML cells and the CML-derived cell lines K562 and KU812. To investigate the role of MCL-1 as a survival-related target in CML cells, mcl-1 siRNA and mcl-1 antisense oligonucleotides (ASOs) were applied. The resulting down-regulation of MCL-1 was found to be associated with a substantial decrease in viability of K562 cells. Moreover, the mcl-1 ASO was found to synergize with imatinib in producing growth inhibition in these cells. Together, our data identify MCL-1 as a BCR/ABL-dependent survival factor and interesting target in CML. (Blood. 2005;105:3303-3311)
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
J. G. Harb, B. I. Chyla, and C. S. Huettner
Loss of Bcl-x in Ph+ B-ALL increases cellular proliferation and does not inhibit leukemogenesis
Blood,
April 1, 2008;
111(7):
3760 - 3769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Copland, F. Pellicano, L. Richmond, E. K. Allan, A. Hamilton, F. Y. Lee, R. Weinmann, and T. L. Holyoake
BMS-214662 potently induces apoptosis of chronic myeloid leukemia stem and progenitor cells and synergizes with tyrosine kinase inhibitors
Blood,
March 1, 2008;
111(5):
2843 - 2853.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Eiring, P. Neviani, R. Santhanam, J. J. Oaks, J. S. Chang, M. Notari, W. Willis, C. Gambacorti-Passerini, S. Volinia, G. Marcucci, et al.
Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesis
Blood,
January 15, 2008;
111(2):
816 - 828.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rahmani, T. K. Nguyen, P. Dent, and S. Grant
The Multikinase Inhibitor Sorafenib Induces Apoptosis in Highly Imatinib Mesylate-Resistant Bcr/Abl+ Human Leukemia Cells in Association with Signal Transducer and Activator of Transcription 5 Inhibition and Myeloid Cell Leukemia-1 Down-Regulation
Mol. Pharmacol.,
September 1, 2007;
72(3):
788 - 795.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Dasmahapatra, N. Yerram, Y. Dai, P. Dent, and S. Grant
Synergistic Interactions between Vorinostat and Sorafenib in Chronic Myelogenous Leukemia Cells Involve Mcl-1 and p21CIP1 Down-Regulation
Clin. Cancer Res.,
July 15, 2007;
13(14):
4280 - 4290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Modi, T. McDonald, S. Chu, J.-K. Yee, S. J. Forman, and R. Bhatia
Role of BCR/ABL gene-expression levels in determining the phenotype and imatinib sensitivity of transformed human hematopoietic cells
Blood,
June 15, 2007;
109(12):
5411 - 5421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. K. Nguyen, M. Rahmani, H. Harada, P. Dent, and S. Grant
MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src inhibitor BMS-354/825
Blood,
May 1, 2007;
109(9):
4006 - 4015.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. M. Greene, L. Kelly, V. Onnis, G. Campiani, M. Lawler, D. C. Williams, and D. M. Zisterer
STI-571 (Imatinib Mesylate) Enhances the Apoptotic Efficacy of Pyrrolo-1,5-Benzoxazepine-6, a Novel Microtubule-Targeting Agent, in Both STI-571-Sensitive and -Resistant Bcr-Abl-Positive Human Chronic Myeloid Leukemia Cells
J. Pharmacol. Exp. Ther.,
April 1, 2007;
321(1):
288 - 297.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nam, A. Williams, A. Vultur, A. List, K. Bhalla, D. Smith, F. Y. Lee, and R. Jove
Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells
Mol. Cancer Ther.,
April 1, 2007;
6(4):
1400 - 1405.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Aichberger, M. Mayerhofer, K. V. Gleixner, M.-T. Krauth, A. Gruze, W. F. Pickl, V. Wacheck, E. Selzer, L. Mullauer, H. Agis, et al.
Identification of MCL1 as a novel target in neoplastic mast cells in systemic mastocytosis: inhibition of mast cell survival by MCL1 antisense oligonucleotides and synergism with PKC412
Blood,
April 1, 2007;
109(7):
3031 - 3041.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. W. Adams and G. M. Cooper
Rapid Turnover of Mcl-1 Couples Translation to Cell Survival and Apoptosis
J. Biol. Chem.,
March 2, 2007;
282(9):
6192 - 6200.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. H. Kaufmann
Imatinib spells BAD news for Bcr/abl-positive leukemias
PNAS,
October 3, 2006;
103(40):
14651 - 14652.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. K. Nguyen, M. Rahmani, N. Gao, L. Kramer, A. S. Corbin, B. J. Druker, P. Dent, and S. Grant
Synergistic interactions between DMAG and mitogen-activated protein kinase kinase 1/2 inhibitors in Bcr/abl+ leukemia cells sensitive and resistant to imatinib mesylate.
Clin. Cancer Res.,
April 1, 2006;
12(7 Pt 1):
2239 - 2247.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rahmani, E. M. Davis, C. Bauer, P. Dent, and S. Grant
Apoptosis Induced by the Kinase Inhibitor BAY 43-9006 in Human Leukemia Cells Involves Down-regulation of Mcl-1 through Inhibition of Translation
J. Biol. Chem.,
October 21, 2005;
280(42):
35217 - 35227.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. J. Aichberger, M. Mayerhofer, M.-T. Krauth, A. Vales, R. Kondo, S. Derdak, W. F. Pickl, E. Selzer, M. Deininger, B. J. Druker, et al.
Low-Level Expression of Proapoptotic Bcl-2-Interacting Mediator in Leukemic Cells in Patients with Chronic Myeloid Leukemia: Role of BCR/ABL, Characterization of Underlying Signaling Pathways, and Reexpression by Novel Pharmacologic Compounds
Cancer Res.,
October 15, 2005;
65(20):
9436 - 9444.
[Abstract]
[Full Text]
[PDF]
|
|
|
| |
