title: Gene dosage effects in chronic lymphocytic leukemia.
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.
authors.affiliation: Department of Hematology, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45122 Essen, Germany. ludger.sellmann@uk-essen.de
authors.forename: Ludger
authors.initials: L
authors.lastname: Sellmann
authors.forename: Rene
authors.initials: R
authors.lastname: Scholtysik
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.forename: Sandra
authors.initials: S
authors.lastname: Cyrull
authors.forename: Enrico
authors.initials: E
authors.lastname: Tiacci
authors.forename: Jens
authors.initials: J
authors.lastname: Stanelle
authors.forename: Alexander
authors.initials: A
authors.lastname: Carpinteiro
authors.forename: Holger
authors.initials: H
authors.lastname: Nückel
authors.forename: Tanja
authors.initials: T
authors.lastname: Boes
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Ulrich
authors.initials: U
authors.lastname: Dührsen
authors.forename: Jan
authors.initials: J
authors.lastname: Dürig
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics; D002874:Chromosome Mapping; D053487:DEAD-box RNA Helicases / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D018628:Gene Dosage; D005786:Gene Expression Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D035683:MicroRNAs / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics; D024182:Uniparental Disomy / Q000235:genetics; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C499217:DDX10 protein, human; D053487:DEAD-box RNA Helicases