title: Changes associated with lenalidomide treatment in the gene expression profiles of patients with del(5q).
abstract: We used microarray profiling to investigate the direct effects of lenalidomide on gene expression in isolated CD14(+) monocytes from 6 patients with del(5q). Our data demonstrate that changes in genes involved the tumor necrosis factor (TNF) signaling pathway and the bone marrow stroma, suggesting that treatment with lenalidomide may help restore the damaged niche and suppress the TNF signaling pathway.
  
  
  BACKGROUND
  Lenalidomide is an effective treatment for patients with del(5q) and myelodysplastic syndrome (MDS) The exact mechanism of lenalidomide function and its impact on the prognosis of patients is not known exactly.
  
  
  METHODS
  We used gene expression profiling to study the effect of lenalidomide therapy in peripheral blood CD14(+) monocytes of 6 patients with del(5q) and MDS.
  
  
  RESULTS
  After lenalidomide treatment, genes involved in the tumor necrosis factor (TNF) signaling pathway that were upregulated in the patients before treatment decreased to the healthy control baseline expression level. This change in gene expression, in conjunction with increased expression of repressed genes that affect the stem cell niche (ie, CXCR4 and CRTAP), may exert a positive effect on treated patients. In contrast, we found that increased expression of the ARPC1B gene may have a negative impact on the stability of patient remission.
  
  
  CONCLUSIONS
  The observed changes in gene expression described here may contribute to the identification of pathways that are affected by lenalidomide, which may help to explain the effects of this drug.
authors.affiliation: Institute of Hematology and Blood Transfusion, Prague, Czech Republic. monika.belickova@uhkt.cz
authors.forename: Monika
authors.initials: M
authors.lastname: Belickova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cermak
authors.forename: Michaela
authors.initials: M
authors.lastname: Dostalova Merkerova
authors.forename: Jitka
authors.initials: J
authors.lastname: Vesela
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Krejcik
authors.forename: Eliska
authors.initials: E
authors.lastname: Cechova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zemanova
authors.forename: Kyra
authors.initials: K
authors.lastname: Michalova
authors.forename: Hana
authors.initials: H
authors.lastname: Votavova
authors.forename: Miroslav
authors.initials: M
authors.lastname: Caniga
authors.forename: Radana
authors.initials: R
authors.lastname: Neuwirtova
authors.forename: Anna
authors.initials: A
authors.lastname: Jonasova
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism; D000368:Aged; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D000077269:Lenalidomide; D018950:Lipopolysaccharide Receptors / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D055153:Stem Cell Niche / Q000187:drug effects / Q000235:genetics; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D059467:Transcriptome / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C460821:ARPC1B protein, human; D051376:Actin-Related Protein 2-3 Complex; D053583:Interleukin-1beta; D018950:Lipopolysaccharide Receptors; D016755:Proto-Oncogene Proteins c-jun; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D000077269:Lenalidomide