Department of Hematology/Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, Guangzhou, China.
Cancer. 2024 Mar 15;130(6):973-984. doi: 10.1002/cncr.35129. Epub 2023 Nov 29.
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. IKZF3 (IKAROS family zinc finger 3) is a hematopoietic-specific transcription factor, and it has been validated that it is involved in leukemia. However, the role of IKZF3 single-nucleotide polymorphisms (SNPs) remains unclear. In this case-control study, the authors investigated the association of IKZF3 SNPs with ALL in children.
Six IKZF3 reference SNPs (rs9635726, rs2060941, rs907092, rs12946510, rs1453559, and rs62066988) were genotyped in 692 patients who had ALL (cases) and in 926 controls. The associations between IKZF3 polymorphisms and ALL risk were determined using odds ratios (ORs) and 95% confidence intervals (CIs). The associations of rs9635726 and rs2060941 with the risk of ALL were further estimated by using false-positive report probability (FPRP) analysis. Functional analysis in silico was performed to evaluate the probability that rs9635726 and rs2060941 might influence the regulation of IKZF3.
The authors observed that rs9635726C>T (adjusted OR, 1.49; 95% CI, 1.06-2.11; p = .023) and rs2060941G>T (adjusted OR, 1.51; 95% CI, 1.24-1.84; p = .001) were related to and increased risk of ALL in the recessive and dominant models, respectively. Furthermore, the associations of both rs9635726 (FPRP = .177) and rs2060941 (FPRP < .001) with ALL were noteworthy in the FPRP analysis. Functional analysis indicated that rs9635726 and rs2060941 might repress the transcription of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21.
This study revealed that IKZF3 polymorphisms were associated with increased ALL susceptibility in children and might influence the expression of IKZF3 by disrupting its binding to MLLT1, TAF1, POLR2A, and/or RAD21. IKZF3 polymorphisms were suggested as a biomarker for childhood ALL.
急性淋巴细胞白血病（ALL）是儿童中最常见的癌症。IKZF3（Ikaros 家族锌指蛋白 3）是一种造血特异性转录因子，已有研究证实其与白血病有关。然而，IKZF3 单核苷酸多态性（SNPs）的作用仍不清楚。在这项病例对照研究中，作者研究了 IKZF3 SNPs 与儿童 ALL 的相关性。
在 692 名 ALL 患者（病例）和 926 名对照中，对 6 个 IKZF3 参考 SNPs（rs9635726、rs2060941、rs907092、rs12946510、rs1453559 和 rs62066988）进行了基因分型。使用比值比（OR）和 95%置信区间（CI）来确定 IKZF3 多态性与 ALL 风险之间的关联。使用假阳性报告概率（FPRP）分析进一步估计 rs9635726 和 rs2060941 与 ALL 风险的关系。进行了计算机模拟的功能分析，以评估 rs9635726 和 rs2060941 可能影响 IKZF3 调控的可能性。
作者发现 rs9635726C>T（调整后的 OR，1.49；95%CI，1.06-2.11；p=0.023）和 rs2060941G>T（调整后的 OR，1.51；95%CI，1.24-1.84；p=0.001）在隐性和显性模型中分别与 ALL 风险增加相关。此外，在 FPRP 分析中，rs9635726（FPRP=0.177）和 rs2060941（FPRP<0.001）与 ALL 的关联均具有统计学意义。功能分析表明，rs9635726 和 rs2060941 可能通过破坏其与 MLLT1、TAF1、POLR2A 和/或 RAD21 的结合来抑制 IKZF3 的转录。
本研究表明，IKZF3 多态性与儿童 ALL 易感性增加相关，可能通过破坏其与 MLLT1、TAF1、POLR2A 和/或 RAD21 的结合来影响 IKZF3 的表达。IKZF3 多态性可作为儿童 ALL 的生物标志物。
