title: Imatinib therapy of chronic myeloid leukemia restores the expression levels of key genes for DNA damage and cell-cycle progression.
abstract: BACKGROUND
  Chronic myeloid leukemia (CML) is a malignant clonal disorder of the hematopoietic system caused by the expression of the BCR/ABL fusion oncogene. It is well known that CML cells are genetically unstable. However, the mechanisms by which these cells acquire genetic alterations are poorly understood. Imatinib mesylate is the standard therapy for newly diagnosed CML patients. Imatinib mesylate targets the oncogenic kinase activity of BCR-ABL.
  
  
  OBJECTIVE
  To study the gene expression profile of bone marrow hematopoietic cells in the same patients with CML before and 1 month after imatinib therapy.
  
  
  METHODS
  Samples from patients with CML were analyzed using Affymetrix GeneChip Expression Arrays.
  
  
  RESULTS
  A total of 594 differentially expressed genes, most of which (393 genes) were downregulated, as a result of imatinib therapy were observed.
  
  
  CONCLUSIONS
  The blockade of oncoprotein Bcr-Abl by imatinib could cause a decrease in the expression of key DNA repair genes and substantially modify the expression profile of the bone marrow cells in the first days of therapy.
authors.affiliation: Institute of Biomedicine of Salamanca, Institute of Molecular and Cellular Biology of Cancer, Center of Cancer Research, University of Salamanca-CSIC, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Benito
authors.forename: Eva
authors.initials: E
authors.lastname: Lumbreras
authors.forename: María
authors.initials: M
authors.lastname: Abáigar
authors.forename: Norma C
authors.initials: NC
authors.lastname: Gutiérrez
authors.forename: Manuel
authors.initials: M
authors.lastname: Delgado
authors.forename: Cristina
authors.initials: C
authors.lastname: Robledo
authors.forename: Juan L
authors.initials: JL
authors.lastname: García
authors.forename: Ana E
authors.initials: AE
authors.lastname: Rodríguez-Vicente
authors.forename: M Consuelo
authors.initials: MC
authors.lastname: Cañizo
authors.forename: Jesús Maria Hernández
authors.initials: JM
authors.lastname: Rivas
mesh_terms: D000293:Adolescent; D000328:Adult; D001549:Benzamides; D001854:Bone Marrow Cells / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D018797:Cell Cycle Proteins; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl