Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia
Birgit Kainz
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorMedhat Shehata
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
K. Landsteiner Institute for Cytokine and Tumor Microenvironment, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorMartin Bilban
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorDirk Kienle
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorDaniel Heintel
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorElisabeth Krömer-Holzinger
Department of Human Genetics, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorTrang Le
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAlexander Kröber
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorGerwin Heller
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorIlse Schwarzinger
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorDita Demirtas
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
K. Landsteiner Institute for Cytokine and Tumor Microenvironment, Vienna, Austria
Search for more papers by this authorAndreas Chott
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorHartmut Döhner
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorSabine Zöchbauer-Müller
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorChrista Fonatsch
Department of Human Genetics, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorChristoph Zielinski
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
Search for more papers by this authorStephan Stilgenbauer
Department of Internal Medicine III, University of Ulm, Ulm, Germany
German CLL Study Group
Search for more papers by this authorAlexander Gaiger
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorOswald Wagner
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
Search for more papers by this authorCorresponding Author
Ulrich Jäger
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
German CLL Study Group
Fax: +43-1-40400-4030.
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaSearch for more papers by this authorBirgit Kainz
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorMedhat Shehata
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
K. Landsteiner Institute for Cytokine and Tumor Microenvironment, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorMartin Bilban
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
The first three authors contributed equally to this work.
Search for more papers by this authorDirk Kienle
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorDaniel Heintel
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorElisabeth Krömer-Holzinger
Department of Human Genetics, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorTrang Le
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorAlexander Kröber
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorGerwin Heller
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorIlse Schwarzinger
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorDita Demirtas
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
K. Landsteiner Institute for Cytokine and Tumor Microenvironment, Vienna, Austria
Search for more papers by this authorAndreas Chott
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorHartmut Döhner
Department of Internal Medicine III, University of Ulm, Ulm, Germany
Search for more papers by this authorSabine Zöchbauer-Müller
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorChrista Fonatsch
Department of Human Genetics, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorChristoph Zielinski
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
Search for more papers by this authorStephan Stilgenbauer
Department of Internal Medicine III, University of Ulm, Ulm, Germany
German CLL Study Group
Search for more papers by this authorAlexander Gaiger
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Search for more papers by this authorOswald Wagner
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
Search for more papers by this authorCorresponding Author
Ulrich Jäger
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria
Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria
German CLL Study Group
Fax: +43-1-40400-4030.
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaSearch for more papers by this authorAbstract
We report high expression of the maternally imprinted gene PEG10 in high-risk B-CLL defined by high LPL mRNA expression. Differential expression was initially identified by microarray analysis and confirmed by real time PCR in 42 B-CLL patients. mRNA expression ranged from 0.3- to 375.4-fold compared to normal peripheral blood mononuclear cells (PBMNC). Expression levels in CD19+ B-CLL cells were 100-fold higher than in B-cells from healthy donors. PEG10 expression levels in B-CLL patient samples remained stable over time even after chemotherapy. High PEG10 expression correlated with high LPL expression (p = 0.001) and a positive Coombs' test (p = 0.04). Interestingly, similar expression patterns were observed for the neighbouring imprinted gene sarcoglycan-ε (SGCE). Monoallelic expression and maintained imprinting of PEG10 were found by allele- or methylation-specific PCR. The intensity of intracellular staining of PEG10 protein corresponded to mRNA levels as confirmed by immunofluorescence staining. Short term knock-down of PEG10 in B-CLL cells and HepG2 cells was not associated with changes in cell survival but resulted in a significant change in the expression of 80 genes. However, long term inhibition of PEG10 led to induction of apoptosis in B-CLL cells. Our data indicate (i) a prognostic value of PEG10 in B-CLL patients; (ii) specific deregulation of the imprinted locus at 7q21 in high-risk B-CLL; (iii) a potential functional and biological role of PEG10 protein expression. Altogether, PEG10 represents a novel marker in B-CLL. © 2007 Wiley-Liss, Inc.
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