title: Expression profiles of signal transduction genes in ex vivo drug-resistant pediatric acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Identification of signal transduction genes related to drug resistance in pediatric acute lymphoblastic leukemia (ALL).
  
  
  METHODS
  Ex vivo drug resistance in 107 children, divided into study and validation groups, was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) drug resistance assay. The gene expression profile was identified by microarray analysis and validated by quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  A set of five genes involved in signal transduction, present in each resistance profile, was identified. The expression of four genes was up-regulated: Gardner-Rasheed feline sarcoma viral oncogene homolog, v-Fgr (FGR), S100 calcium binding protein A11 (S100A11), formyl peptide receptor 1 (FPR1), ArfGAP with RhoGAP domain, ankyrin repeat and PH1 domain (ARAP1), while the expression of growth hormone 1 (GH1) was found to be down-regulated in resistant leukemia blasts.
  
  
  CONCLUSIONS
  Ex vivo exposure of leukemia cells to anticancer drugs induces changes in the expression of genes involved in cell signaling pathways. These genes play an important role in the mechanism of cellular drug resistance.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanek
authors.forename: Monika
authors.initials: M
authors.lastname: Pogorzala
authors.forename: Michal
authors.initials: M
authors.lastname: Jarzab
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Oczko-Wojciechowska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kowalska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Tretyn
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
authors.forename: Barbara
authors.initials: B
authors.lastname: Jarzab
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
mesh_terms: D002648:Child; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*