title: [Clinical observation of chromosomal abnormalities in Ph negative cells of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors].
abstract: OBJECTIVE
  To observe the clinical features, characteristics and outcomes of chromosomal abnormalities in Philadelphia negative cells (Ph(-)CA) of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI), and provide the evidence for clinical treatment.
  
  
  METHODS
  We collected and analyzed the clinical and laboratory data of 8 CML patients treated in the affiliated Tumor Hospital of Zhengzhou University from September 2011 to July 2015 and Ph(-)CA occurred after TKI therapy. Karyotypes and BCR-ABL fusion genes were analyzed by R-banding and real-time quantitative polymerase chain reaction (RT-PCR), respectively.
  
  
  RESULTS
  6 cases were male and 2 cases were female, with a median age of 51 (31-75) years old. 6 patients had low Sokal risk scores and 2 had intermediate scores. 4 cases of Ph(-) CA occurred with imatinib, 1 case with dasatinib and 3 cases with nilotinib. The median duration of Ph(-) CA appearance was 12.0 (1.7-34.5) months since taking TKI. Chromosomal abnormality +8 was the most common type in Ph(-)CA, which accounted for 50.0%, followed by -7 (25.0%). When found Ph(-)CA, all patients had complete hematologic response (CHR), but none got main molecular response (MMR). The Ph(-)CA had gone in 7 cases at the end of follow-up and the median duration was 6.2 (2.5-31.5) months. After Ph(-) CA disappeared, 1 patient obtained MMR and 2 cases achieved complete molecular response (CMR), but Ph(+) clone recurred in 1 case.
  
  
  CONCLUSIONS
  Ph(-)CA can be found in CML patients treated with imatinib, dasatinib and nilotinib, and +8 is the most common Ph(-)CA. So detection of karyotype is significant during treatment. Although most Ph(-)CA can disappear, -7/7q- or other complex karyotypes should be monitored closely.
authors.affiliation: Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou 450008, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: Y L
authors.initials: YL
authors.lastname: Zu
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: Y P
authors.initials: YP
authors.lastname: Song
mesh_terms: D000328:Adult; D000368:Aged; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D000069439:Dasatinib / Q000627:therapeutic use; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D059785:Karyotype; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib; D000069439:Dasatinib