title: Identification of the genes expression profile associated with the ex vivo resistance to etoposide in childhood acute leukemias.
abstract: BACKGROUND
  Drug resistance and the gene expression profiles might discriminate the therapy outcome, and indicate the subgroup of patients with poor prognosis. In this study we analyzed the gene expression profile in correlation with the profile of ex vivo resistance to etoposide in children with acute leukemias.
  
  
  METHODS
  The ex vivo drug resistance profile was determined by the MTT cytotoxicity assay performed on leukemic blasts of 56 patients. Gene expression profiles were obtained from the results of hybridization of cRNA to Human Genome U133A 2.0 ologonucleotide arrays. The following analyses were performed: correlation analysis, hierarchical clustering, the assignment of location and function. Verification of data for four selected genes (MNDA, GH1, NUDT21, RHOG) was performed by quantitative real time polymerase chain reaction in the studied population and in an independent group of 54 leukemic patients.
  
  
  RESULTS
  Using the permutation Spearman correlation test, a set of 233 probes/209 genes was selected. The global test confirmed the significance of the correlation of gene expression profile and resistance to etoposide (p<0.001). The NUDT21 (nudix, nucleoside diphosphate linked moiety X-type, motif 21) gene showed the strongest correlation with resistance to etoposide (FDR<0.0001%).
  
  
  CONCLUSIONS
  Profiling of transcriptome may help in assessing the sensitivity to drugs used in chemotherapy. Resistance to etoposide is possibly associated with a change of expression of a large number of biologically important genes that influence several cellular mechanisms.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. szczepanekjoanna@gmail.com
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanek
authors.forename: Jan
authors.initials: J
authors.lastname: Styczyński
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tretyn
authors.forename: Monika
authors.initials: M
authors.lastname: Pogorzała
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
mesh_terms: D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002648:Child; D039223:Cleavage And Polyadenylation Specificity Factor / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010926:Placental Hormones / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D000972:Antineoplastic Agents, Phytogenic; D039223:Cleavage And Polyadenylation Specificity Factor; C064980:GH2 protein, human; C075373:MNDA protein, human; C580829:Nudt21 protein, human; D010926:Placental Hormones; D014157:Transcription Factors; C075397:RHOG protein, human; D005047:Etoposide; D013006:Growth Hormone; D020741:rho GTP-Binding Proteins