title: Translational profiling in childhood acute lymphoblastic leukemia: no evidence for glucocorticoid regulation of mRNA translation.
abstract: BACKGROUND
  Glucocorticoids (GCs) are natural stress induced steroid hormones causing cell cycle arrest and cell death in lymphoid tissues. Therefore they are the central component in the treatment of lymphoid malignancies, in particular childhood acute lymphoblastic leukemia (chALL). GCs act mainly via regulating gene transcription, which has been intensively studied by us and others. GC control of mRNA translation has also been reported but has never been assessed systematically. In this study we investigate the effect of GCs on mRNA translation on a genome-wide scale.
  
  
  RESULTS
  Childhood T- (CCRF-CEM) and precursor B-ALL (NALM6) cells were exposed to GCs and subjected to "translational profiling", a technique combining sucrose-gradient fractionation followed by Affymetrix Exon microarray analysis of mRNA from different fractions, to assess the translational efficiency of the expressed genes. Analysis of GC regulation in ribosome-bound fractions versus transcriptional regulation revealed no significant differences, i.e., GC did not entail a significant shift between ribosomal bound and unbound mRNAs.
  
  
  CONCLUSIONS
  In the present study we analyzed for the first time possible effects of GC on the translational efficiency of expressed genes in two chALL model systems employing whole genome polysome profiling. Our results did not reveal significant differences in translational efficiency of expressed genes thereby arguing against a potential widespread regulatory effect of GCs on translation at least in the investigated in vitro systems.
authors.affiliation: Division of Molecular Pathophysiology, Biocenter, Innsbruck Medical University, Innsbruck 6020, Austria. johannes.rainer@i-med.ac.at.
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Aneichyk
authors.forename: Daniel
authors.initials: D
authors.lastname: Bindreither
authors.forename: Christine
authors.initials: C
authors.lastname: Mantinger
authors.forename: Daniela
authors.initials: D
authors.lastname: Grazio
authors.forename: Katrin
authors.initials: K
authors.lastname: Goetsch
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kofler
authors.forename: Johannes
authors.initials: J
authors.lastname: Rainer
mesh_terms: D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015894:Genome, Human; D005938:Glucocorticoids / Q000502:physiology*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger