Significance of IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia in children
ZOU Yao, LIU Xiao-Ming, ZHANG Li, CHEN Yu-Mei, GUO Ye, CHEN Xiao-Juan, YANG Wen-Yu, WANG Shu-Chun, RUAN Min, LIU Tian-Feng, ZHANG Jia-Yuan, LIU Fang, QI Ben-Quan, ZHU Xiao-Fan
Pediatric Blood Disease Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin 300020, China
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 (PConclusions 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.
About author:: 10.7499/j.issn.1008-8830.2015.11.002
Cite this article:
ZOU Yao,LIU Xiao-Ming,ZHANG Li et al. Significance of IKZF1 gene copy number abnormalities in BCR/ABL-negative B-lineage acute lymphoblastic leukemia in children[J]. CJCP, 2015, 17(11): 1154-1159.
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