Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high-risk B-cell chronic lymphocytic leukemia.
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-epsilon (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.
Kainz
Birgit
B
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Shehata
Medhat
M
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.
Bilban
Martin
M
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Kienle
Dirk
D
Department of Internal Medicine III, University of Ulm, Ulm, Germany.
Heintel
Daniel
D
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Krömer-Holzinger
Elisabeth
E
Department of Human Genetics, Medical University of Vienna, Vienna, Austria.
Le
Trang
T
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Kröber
Alexander
A
Department of Internal Medicine III, University of Ulm, Ulm, Germany.
Heller
Gerwin
G
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Schwarzinger
Ilse
I
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Demirtas
Dita
D
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.
Chott
Andreas
A
Department of Clinical Pathology, Medical University of Vienna, Vienna, Austria.
Döhner
Hartmut
H
Department of Internal Medicine III, University of Ulm, Ulm, Germany.
Zöchbauer-Müller
Sabine
S
Division of Oncology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Fonatsch
Christa
C
Department of Human Genetics, Medical University of Vienna, Vienna, Austria.
Zielinski
Christoph
C
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.
Stilgenbauer
Stephan
S
Department of Internal Medicine III, University of Ulm, Ulm, Germany.|German CLL Study Group.
Gaiger
Alexander
A
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
Wagner
Oswald
O
Department of Clinical Chemistry and Laboratory Medicine, Medical University of Vienna, Vienna, Austria.|Center of Excellence in Clinical and Experimental Oncology (CLEXO), Vienna, Austria.
Jäger
Ulrich
U
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.
D000483:Alleles; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D019175:DNA Methylation; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting / Q000235:genetics*; D006262:Health; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D011134:Polysaccharides / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D012307:Risk Factors; D015996:Survival Rate; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D000098563:Seven in Absentia Proteins
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C432965:PEG10 protein, human; D011134:Polysaccharides; D011506:Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins