Granados-Zamora Melissa, Chaves-Herrera Karla, Morera-Araya Estela, Granados-Alfaro Paola, Valverde-Muñoz Kathia, Soto-Herrera Gabriela, Santamaría-Quesada Carlos
Clinical Analysis Department, Faculty of Microbiology, University of Costa Rica.
Hematology Department.
J Pediatr Hematol Oncol. 2020 Aug;42(6):e401-e406. doi: 10.1097/MPH.0000000000001807.
The IKZF1 gene encodes for Ikaros, a transcriptional factor in B-cell development. Deletions in this gene have been associated with a worse prognosis in B-cell acute lymphoblastic leukemia (B-ALL). We evaluated the presence of these alterations in all Costa Rican pediatric patients diagnosed with B-ALL between 2011 and 2014, treated with a modified Berlin-Frankfurt-Münster therapeutic protocol. Multiplex polymerase chain reaction with 2 detection methods (agarose gel and gene scanning) was used to detect intragenic deletions and multiplex ligation-dependent probe amplification for whole-gene deletions. Differences between groups (normal vs. deleted IKZF1) were analyzed by the χ test, the Kaplan-Meier test was used to calculate relapse-free survival and overall survival, and Cox regression was performed for multivariant analysis. Minimum follow-up was 4.5 years. Incidence of IKZF1 deletions was 12.9% (n=20), with an equal amount of intragenic and complete gene deletions. Adverse karyotype (P=0.048), high-risk category (P=0.030), occurrence of relapse (P=0.021), and medullar relapse (P=0.011) were statistically associated with the presence of deletions in IKZF1. Relapse-free survival at 54 months was lower in patients harboring an IKZF1 deletion than that in patients with IKZF1-wt (40.0% vs. 66.7%; P=0.014). Patients with B-ALL and IKZF1 deletions, showed a poorer relapse-free survival, in comparison with patients with IKZF1-wt, suggesting that IKZF1 status is an independent prognostic factor for pediatric patients with B-ALL.
IKZF1基因编码Ikaros，它是B细胞发育过程中的一种转录因子。该基因的缺失与B细胞急性淋巴细胞白血病（B-ALL）的预后较差有关。我们评估了2011年至2014年间所有诊断为B-ALL并采用改良柏林-法兰克福-明斯特治疗方案治疗的哥斯达黎加儿科患者中这些改变的存在情况。采用两种检测方法（琼脂糖凝胶和基因扫描）的多重聚合酶链反应来检测基因内缺失，并用多重连接依赖探针扩增法检测全基因缺失。通过χ检验分析组间差异（正常组与IKZF1缺失组），采用Kaplan-Meier检验计算无复发生存率和总生存率，并进行Cox回归进行多变量分析。最短随访时间为4.5年。IKZF1缺失的发生率为12.9%（n = 20），基因内缺失和全基因缺失的数量相等。不良核型（P = 0.048）、高危类别（P = 0.030）、复发的发生（P = 0.021）和髓系复发（P = 0.011）与IKZF1缺失的存在在统计学上相关。IKZF1缺失患者54个月时的无复发生存率低于IKZF1野生型患者（40.0%对66.7%；P = 0.014）。与IKZF1野生型患者相比，B-ALL和IKZF1缺失患者的无复发生存率较差，这表明IKZF1状态是B-ALL儿科患者的一个独立预后因素。
