Department of Pediatric Oncology, ACTREC/Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, 400 012, Maharashtra, India.
Department of Pediatric Oncology and BMT, Great North Children's Hospital, Royal Victoria Infirmary, Newcastle Upon Tyne, United Kingdom.
Ann Hematol. 2023 Aug;102(8):2165-2179. doi: 10.1007/s00277-023-05250-1. Epub 2023 May 8.
IKZF1 (IKAROS family Zinc Finger 1) alteration is an essential regulator of both T- and B-cell lineage specification with leukemogenic potential. IKZF1 deletion have been described in childhood acute lymphoblastic leukemia (ALL) with varying prevalence often influenced by underlying cytogenetics and also shown to have diverse prognostic significance. We aimed to evaluate the prevalence and prognostic significance of IKZF1 deletion among childhood ALL. Electronic databases of MEDLINE, EMBASE and SCOPUS were searched and 32 studies found eligible. Estimated prevalence of IKZF1 deletion among BCR::ABL1 negative and BCR::ABL1 positive ALL patients was 14% (95%CI:13-16%, I = 79%; 26 studies) and 63% (95%CI:59-68% I = 42%; 10 studies) respectively. Most common site of IKZF1 deletion was whole chromosome (exon1-8) deletion in 32.3% (95%CI: 23.8-40.7%) followed by exon 4-7 deletion in 28.6% (95%CI: 19.7-37.5%). A positive minimal residual disease at the end of induction was more common among patients with IKZF1 deletion, odds ratio: 3.09 (95%CI:2.3-4.16, I = 54%; 15 studies). Event-free survival and overall survival were significantly worse for IKZF1 deletion, hazard ratio (HR): 2.10 (95%CI:1.90-2.32, I = 28%; 31 studies) and HR: 2.38 (95%CI:1.93-2.93, I = 40; 15 studies) respectively. In summary, the current meta-analysis highlights the frequency of IKZF1 deletion and its negative impact on survival in childhood ALL. Further studies exploring the influence of IKZF1 deletion in the presence of classical cytogenetic and other copy number alterations would further help in characterising its prognostic role.
IKZF1（IKAROS 家族锌指蛋白 1）改变是 T 细胞和 B 细胞谱系特异性的重要调节因子，具有白血病发生潜能。IKZF1 缺失已在儿童急性淋巴细胞白血病（ALL）中被描述，其发生率因潜在的细胞遗传学而异，并且具有不同的预后意义。我们旨在评估 IKZF1 缺失在儿童 ALL 中的发生率和预后意义。检索了 MEDLINE、EMBASE 和 SCOPUS 的电子数据库，发现了 32 项符合条件的研究。在 BCR::ABL1 阴性和 BCR::ABL1 阳性 ALL 患者中，IKZF1 缺失的估计发生率分别为 14%（95%CI：13-16%，I=79%；26 项研究）和 63%（95%CI：59-68%，I=42%；10 项研究）。IKZF1 缺失最常见的部位是整条染色体（外显子 1-8）缺失，占 32.3%（95%CI：23.8-40.7%），其次是外显子 4-7 缺失，占 28.6%（95%CI：19.7-37.5%）。在诱导结束时存在微小残留病阳性的患者中，IKZF1 缺失更为常见，优势比：3.09（95%CI：2.3-4.16，I=54%；15 项研究）。事件无进展生存和总生存对 IKZF1 缺失的影响明显较差，风险比（HR）：2.10（95%CI：1.90-2.32，I=28%；31 项研究）和 HR：2.38（95%CI：1.93-2.93，I=40%；15 项研究）。总之，本荟萃分析强调了 IKZF1 缺失在儿童 ALL 中的频率及其对生存的负面影响。进一步研究探索 IKZF1 缺失在经典细胞遗传学和其他拷贝数改变存在时的影响，将有助于进一步阐明其预后作用。
