title: Altered expression of autophagy-related genes might contribute to glucocorticoid resistance in precursor B-cell-type acute lymphoblastic leukemia.
abstract: OBJECTIVE
  Autophagy is an evolutionarily conserved process playing an important role in tumor cell's resistance to chemotherapy. Response to glucocorticoid (GC) treatment is out of the most important prognostic factors in childhood acute lymphoblastic leukemia (ALL); however, only few data are available connecting GC response and role of autophagy. Our aim was to investigate whether altered expression of autophagy-related genes contributes to GC-resistant phenotype in GC-sensitive and GC-resistant precursor B-cell-type (PBC) ALL cells.
  
  
  METHODS
  Gene expression data were obtained from public database for 26 children diagnosed with PBC ALL either sensitive or resistant to in vitro prednisolone treatment.
  
  
  RESULTS
  We have identified 36 autophagy-associated genes which were differently expressed, based on at least a twofold difference, GC-sensitive group as compared to GC-resistant one. Of the 36 genes, 10 were downregulated and 26 upregulated in the GC-resistant group. The average fold change values for the decreased and increased transcripts were -4.57 and 2.67, respectively.
  
  
  CONCLUSIONS
  Our data imply that GC sensitivity might depend on the expression of several genes involved in regulation and execution of autophagy in a way that key autophagy inducers are downregulated while inhibitors of autophagy are upregulated in GC-resistant cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Clinical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Sarang
authors.affiliation: Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Clinical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Gyurina
authors.affiliation: Department of Clinical Genomics, Clinical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Scholtz
authors.affiliation: Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Clinical Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Csongor
authors.initials: C
authors.lastname: Kiss
authors.affiliation: Department of Pediatric Hematology-Oncology, Institute of Pediatrics, Clinical Center, University of Debrecen, Debrecen, Hungary. iszegedi@dote.hu.
authors.forename: István
authors.initials: I
authors.lastname: Szegedi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001343:Autophagy / Q000235:genetics*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods; D030561:Databases, Nucleic Acid; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D005938:Glucocorticoids
keywords: acute lymphoblastic leukemia; autophagy; childhood; gene expression; glucocorticoid sensitivity