Gene dosage effects in chronic lymphocytic leukemia |
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| Authors: | Sellmann Ludger Scholtysik Rene Kreuz Markus Cyrull Sandra Tiacci Enrico Stanelle Jens Carpinteiro Alexander Nückel Holger Boes Tanja Gesk Stefan Siebert Reiner Klein-Hitpass Ludger Dührsen Ulrich Dürig Jan Küppers Ralf |
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| Affiliation: | aDepartment of Hematology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany;bInstitute of Cell Biology (Cancer Research), Medical Faculty, University of Duisburg-Essen, Virchowstraße 173, 45122 Essen, Germany;cInstitute of Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Härtelstraße 16-18, 04107 Leipzig, Germany;dDepartment of Paedriatics, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany;eInstitute of Hematology, Hematopathology Section, 06132 Perugia, Italy;fInstitute for Medical Informatics, Biometry and Epidemiology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany;gInstitute of Human Genetics, Christian-Albrechts-University Kiel, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 24, 24105 Kiel, Germany |
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| Abstract: | To understand the influence of chromosomal alterations on gene expression in a genome-wide view, chromosomal imbalances detected by single nucleotide polymorphism (SNP) chips were compared with global gene expression in 16 cases of chronic lymphocytic leukemia (CLL). A strong concordance between chromosomal gain or loss and increased or reduced expression of genes in the affected regions was found, respectively. Regions of uniparental disomy (UPD) were rare and had usually no consistent influence on gene expression, but in one instance, a large UPD was associated with a downregulation of most genes in the affected chromosome. The frequently deleted miRNAs, MIRN15A and MIRN16-1, did not show a reduced expression in cases with monoallelic deletions. The BCL2 protein, considered to be downregulated by these miRNAs, was upregulated not only in CLL with biallelic deletion of MIRN15A and MIRN16-1, but also in cases with monoallelic deletion. This suggests a complex regulation of BCL2 levels in CLL cells. Taken together, in CLL, a global gene dosage effect exists for chromosomal gains and deletions and in some instances for UPDs. We did not confirm a consistent correlation between MIRN15A and MIRN16-1 expression levels and BCL2 protein levels, indicating a complex regulation of BCL2 expression. |
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