title: [Significance of IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia in children].
abstract: OBJECTIVE
  To identify IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia (B-ALL) in children, and to investigate the association between such abnormalities and prognosis.
  
  
  METHODS
  Multiplex ligation-dependent probe amplification (MLPA) was applied to detect IKZF1 gene copy number abnormalities in 180 children diagnosed with BCR/ABL-negative B-ALL. These children were classified into IKZF1 deletion group and IKZF1 normal group according to the presence or absence of IKZF1 gene deletion. The association between IKZF1 copy number abnormalities and prognosis of children with BCR/ABL-negative B-ALL was analyzed retrospectively.
  
  
  RESULTS
  Among 180 children, 27 (15.0%) had IKZF1 deletion; among the 27 children, 4 had complete deletions of 8 exons of IKZF1 gene, 17 had deletion of exon 1, 3 had deletions of exons 4-7, and 3 children had deletions of exons 2-7. Compared with those in the IKZF1 normal group, children in the IKZF1 deletion group had higher white blood cell (WBC) count and percentage of individuals with high risk of minimal residual disease at the first visit. IKZF1 deletions often occurred in BCR/ABL-negative children with no special fusion gene abnormalities. They were frequently accompanied by abnormalities in chromosomes 11, 8, 5, 7, and 21. The analysis with Kaplan-Meier method showed that disease-free survival (DFS) in the IKZF1 deletion group was significantly lower than that in the IKZF1 normal group (0.740 ± 0.096 vs 0.905 ± 0.034; P=0.002). Cox analysis showed that after exclusion of sex, age, initial WBC count, cerebrospinal fluid state at the first visit, prednisone response, and chromosome karyotype, IKZF1 deletion still affected the children's DFS (P<0.05).
  
  
  CONCLUSIONS
  Some children with BCR/ABL-negative B-ALL have IKZF1 deletion, and IKZF1 deletion is an independent risk factor for DFS in children with BCR/ABL-negative B-ALL.
authors.affiliation: Pediatric Blood Disease Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China. xfzhu1981@126.com.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zou
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Chen
authors.forename: Ye
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Chen
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Yang
authors.forename: Shu-Chun
authors.initials: SC
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Ruan
authors.forename: Tian-Feng
authors.initials: TF
authors.lastname: Liu
authors.forename: Jia-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Ben-Quan
authors.initials: BQ
authors.lastname: Qi
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000032:analysis*; D018628:Gene Dosage; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis
chemical_list: C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor; D016044:Fusion Proteins, bcr-abl