title: CD117 (c-kit) expression on CD34+ cells participates in the cytogenetic response to imatinib in patients with chronic myeloid leukemia in the first chronic phase.
abstract: BACKGROUND
  Chronic myeloid leukemia (CML) biology seemed to be perfectly explored especially at the beginning of the tyrosine kinase inhibitors era. Later years with imatinib and second-generation tyrosine kinase inhibitors showed a variety of resistance mechanisms and it became obvious that the bcr-abl chimeric gene is not the only enemy to fight. Some studies assumed the decreased rate of programmed cell death (apoptotic) to be the primary mechanism by which BCR-ABL affects expansion of the leukemic clone in CML. Therefore, the aim of this study was to investigate the role of c-kit inhibition in treatment response.
  
  
  METHODS
  Cytogenetic analysis, real-time quantitative reverse-transcriptase polymerase chain reaction, flow-cytometric analysis and imatinib serum level quantification were applied.
  
  
  RESULTS
  The percentage of CD34+ cells expressing c-kit (CD117) isolated from bone marrow samples of 54 CML patients treated with standard-dose imatinib was significantly lower among imatinib responders. The fraction of apoptotic CD34+CD117+ cells in this patient group was significantly higher than in nonresponders.
  
  
  CONCLUSIONS
  To achieve optimal treatment response in CML patients, the elimination of CD34+CD117+ may be necessary through an apoptotic pathway.
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Dybko
authors.forename: Olga
authors.initials: O
authors.lastname: Haus
authors.forename: Bozena
authors.initials: B
authors.lastname: Jazwiec
authors.forename: Joanna
authors.initials: J
authors.lastname: Urbaniak
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Wozniak
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaczmar-Dybko
authors.forename: Donata
authors.initials: D
authors.lastname: Urbaniak-Kujda
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kapelko-Slowik
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Kuliczkowski
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000970:Antineoplastic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001549:Benzamides / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000068877:Imatinib Mesylate; D016130:Immunophenotyping; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D010879:Piperazines / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors* / Q000502:physiology; D011743:Pyrimidines / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D012074:Remission Induction
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; D001549:Benzamides; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit