title: Research on and clinical importance of duplications in various chromosomal regions in addition to Philadelphia chromosome in chronic myeloid leukemia.
abstract: OBJECTIVE
  To investigate the chromosomal aberrations in chronic myelogenous leukemia (CML), particularly in chromosomal regions which carried 67 genes pertaining to oncogenes, transcription factors, signal transduction, tumor suppressors, apoptosis etc, in addition to Philadelphia (Ph+) chromosome by multiplex ligation-dependent probe amplification (MLPA) method and to compare them with clinical parameters.
  
  
  METHODS
  The aberrations were investigated in 48 CML patients receiving imatinib therapy and a group of 15 healthy controls, by using the MLPA method between 2000 and 2009. The obtained results were compared both between patient and control groups and with clinical parameters.
  
  
  RESULTS
  Duplication was detected in the fibroblast growth factor receptor 1 (FGFR1) gene of 2 patients, inosine 5' monophosphate dehydrogenase 1 (IMPDH1) gene of 4, postmeiotic segregation increased S. Cerevisiae 2 (PMS2) gene of 1, nuclear factor kappa beta (NFKB) of 5 and T-cell translocation 2 (LMO2) gene of 1 patient. Univariate analysis showed that splenomegaly, advanced age, Sokal risk score (SRS) and the duplications in IMPDH1 and FGFR1 genes significantly shortened 7-year event-free survival (EFS); multivariate analysis showed that only the duplications in IMPDH1 and FGFR1 genes were the factors that significantly affected EFS. No statistically significant correlations were detected between duplications and other clinical parameters.
  
  
  CONCLUSIONS
  Duplications in 4 genes (FGFR1, IMPDH1, PMS2, LMO2) in addition to Ph+ chromosome in CML patients were detected for the first time. This study indicates that chromosomes 7 and 8 should be particularly investigated in more detail in addition to the Ph+ chromosome for better determination of disease prognosis and selection of alternative treatments.
authors.affiliation: Department of Medical Biology and Genetics, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Sever
authors.forename: C
authors.initials: C
authors.lastname: Kilicarslan
authors.forename: M
authors.initials: M
authors.lastname: Pehlivan
authors.forename: L
authors.initials: L
authors.lastname: Kaynar
authors.forename: M
authors.initials: M
authors.lastname: Yilmaz
authors.forename: B
authors.initials: B
authors.lastname: Eser
authors.forename: V
authors.initials: V
authors.lastname: Okan
authors.forename: F
authors.initials: F
authors.lastname: Kurnaz
authors.forename: M
authors.initials: M
authors.lastname: Cetin
authors.forename: S
authors.initials: S
authors.lastname: Pehlivan
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D058674:Chromosome Duplication; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D007168:IMP Dehydrogenase / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070976:Mismatch Repair Endonuclease PMS2; D010677:Philadelphia Chromosome; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes