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Overexpression of the paternally expressed gene 10 (PEG10) from the imprinted locus on chromosome 7q21 in high‐risk B‐cell chronic lymphocytic leukemia
Author(s) -
Kainz Birgit,
Shehata Medhat,
Bilban Martin,
Kienle Dirk,
Heintel Daniel,
KrömerHolzinger Elisabeth,
Le Trang,
Kröber Alexander,
Heller Gerwin,
Schwarzinger Ilse,
Demirtas Dita,
Chott Andreas,
Döhner Hartmut,
ZöchbauerMüller Sabine,
Fonatsch Christa,
Zielinski Christoph,
Stilgenbauer Stephan,
Gaiger Alexander,
Wagner Oswald,
Jäger Ulrich
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22929
Subject(s) - genomic imprinting , locus (genetics) , biology , chronic lymphocytic leukemia , imprinting (psychology) , genetics , gene , chromosome , leukemia , cancer research , gene expression , dna methylation
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.