title: Gene expression profiles of Hodgkin's lymphoma cell lines with different sensitivity to cytotoxic drugs.
abstract: OBJECTIVE
  The prognosis of patients with Hodgkin's lymphoma (HL) has been significantly improved as a result of combination treatment including chemotherapy. However, some patients are refractory to chemotherapy. Therefore, identification of new targets might be useful for development of alternative treatment strategies. In addition, identification of markers associated with chemoresistance can be used to identify patients with increased risk of relapse.
  
  
  METHODS
  By using high-density DNA microarrays, we analyzed the gene-expression profile of HL-cell lines in comparison to a set of normal tissues. Furthermore, we tested the sensitivity of HL cells for cytotoxic drugs (cisplatin, etoposide, melphalan) and compared the gene-expression profile of chemotherapy-resistant and -sensitive cell lines. Differentially expressed genes were validated by polymerase chain reaction and flow cytometry.
  
  
  RESULTS
  In addition to genes with high expression in all cell lines, we observed differences between the gene-expression profile of chemotherapy-resistant and -sensitive cells. Genes upregulated in resistant cells include cytokine receptors (IL5RA, IL13RA1), markers expressed on antigen-presenting cells (CD40, CD80), as well as genes with known association to chemoresistance, e.g., myristoylated alanine-rich protein kinase C substrate. In addition, the tumor antigen PRAME (preferentially expressed antigen in melanoma) was expressed in resistant cell lines only.
  
  
  CONCLUSIONS
  Genes with high expression in HL cells might be potential targets for development of future therapeutic interventions. Expression of tumor antigens together with costimulatory molecules in chemotherapy-resistant HL cells might become targets for cytotoxic T-cell responses against HL cells.
authors.affiliation: Department of Pediatrics, Children's Cancer Research Center. Martin-Luther-University Halle-Wittenberg, Halle, Germany.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Staege
authors.forename: Ursula
authors.initials: U
authors.lastname: Banning-Eichenseer
authors.forename: Grit
authors.initials: G
authors.lastname: Weissflog
authors.forename: Ines
authors.initials: I
authors.lastname: Volkmer
authors.forename: Stefan
authors.initials: S
authors.lastname: Burdach
authors.forename: Günther
authors.initials: G
authors.lastname: Richter
authors.forename: Christine
authors.initials: C
authors.lastname: Mauz-Körholz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Föll
authors.forename: Dieter
authors.initials: D
authors.lastname: Körholz
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006689:Hodgkin Disease / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis; D055502:Secondary Prevention
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor