title: IKZF1 deletions predict a poor prognosis in children with B-cell progenitor acute lymphoblastic leukemia: a multicenter analysis in Taiwan.
abstract: Despite current risk-directed therapy, approximately 15-20% of pediatric patients with acute lymphoblastic leukemia (ALL) have relapses. Recent genome-wide analyses have identified that an alteration of IKZF1 is associated with very poor outcomes in B-cell progenitor ALL. In this study, we determined the prognostic significance of IKZF1 deletions in patients with childhood ALL. This study analyzed 242 pediatric B-cell progenitor ALL patients in Taiwan. We developed a simple yet sensitive multiplex quantitative PCR coupled with capillary electrophoresis to accurately determine the allele dose of IKZF1, and high resolution melting was used for mutation screening for all coding exons of IKZF1. Twenty-six (10.7%) pediatric B-cell progenitor ALL patients were found to harbor these deletions. Most of the deletions were broader deletions that encompassed exon 3 to exon 6, consistent with previous reports. Genomic sequencing of IKZF1 was carried out in all cases and no point mutations were identified. Patients with IKZF1 deletions had inferior event-free survival (P < 0.001), and overall survival (P = 0.0016). The association between IKZF1 deletions and event-free survival was independent of age, leukocyte count at presentation, and cytogenetic subtype by multivariate Cox analysis (P = 0.003, hazard ratio = 2.45). This study indicates that detection of IKZF1 deletions upon diagnosis of B-cell progenitor ALL may help to identify patients at risk of treatment failure. IKZF1 deletions could be incorporated as a new high-risk prognostic factor in future treatment protocols. To the best of our knowledge, this is the first study to examine the poor prognosis of IKZF1 deletions in an Asian population.
authors: Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors: Yung-Li
authors: YL
authors: Yang
authors: Chia-Cheng
authors: CC
authors: Hung
authors: Jiann-Shiuh
authors: JS
authors: Chen
authors: Kai-Hsin
authors: KH
authors: Lin
authors: Shiann-Tarng
authors: ST
authors: Jou
authors: Chih-Cheng
authors: CC
authors: Hsiao
authors: Jiunn-Ming
authors: JM
authors: Sheen
authors: Chao-Neng
authors: CN
authors: Cheng
authors: Kang-Hsi
authors: KH
authors: Wu
authors: Shu-Rung
authors: SR
authors: Lin
authors: Sung-Liang
authors: SL
authors: Yu
authors: Hsuan-Yu
authors: HY
authors: Chen
authors: Meng-Yao
authors: MY
authors: Lu
authors: Shih-Chung
authors: SC
authors: Wang
authors: Hsiu-Hao
authors: HH
authors: Chang
authors: Shu-Wha
authors: SW
authors: Lin
authors: Yi-Ning
authors: YN
authors: Su
authors: Dong-Tsamn
authors: DT
authors: Lin
mesh_terms: D000293:Adolescent; D001402:B-Lymphocytes; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D013624:Taiwan; D017211:Treatment Failure
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; C497239:IKZF1 protein, human; D051740:Ikaros Transcription Factor