High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations.
High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations.
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白细胞介素 3 受体 α 链 (CD123) 的高表达预示着缺乏预后定义基因组畸变的儿童 B 细胞急性淋巴细胞白血病的良好结果
DOI：
10.3389/fonc.2021.614420
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发表时间：
2021
影响因子：
4.7
通讯作者：
Hu S
中科院分区：
文献类型：
--
作者：
Li Z;Chu X;Gao L;Ling J;Xiao P;Lu J;Wang Y;He H;Li J;Hu Y;Li J;Pan J;Xiao S;Hu S
CD 123（IL-3Rα）异常表达见于多种血液系统恶性肿瘤，包括儿童最常见的恶性肿瘤急性淋巴细胞白血病（ALL）。虽然广泛用于微小残留病（MRD）监测，但CD 123的预后价值尚未在儿科B-ALL中得到充分表征。本回顾性研究旨在评估白血病原始细胞CD 123表达与儿童B-ALL患者预后之间的关系。本回顾性研究共招募了976例儿童B-ALL，其中328例接受CCLG-ALL-2008方案治疗，648例接受CCCG-ALL-2015方案治疗。通过流式细胞术评估CD 123表达。将表达CD 123的原始细胞> 50%、20- 50%或<20%的患者分别分为CD 123高、CD 123低和CD 123阴性。统计分析CD 123表达与患者临床特征、总生存期（OS）、无事件生存期（EFS）和无复发生存期（RFS）的相关性。在976例儿童B-ALL中，53.4%来自CCLG-ALL-2008队列，49.2%来自CCCG-ALL-2015队列。在CCLG-ALL-2008队列中，CD 123 high与染色体超二倍体（p < 0.0001）、风险分层（p = 0.004）和高生存率（p = 0.005）显著相关。通过比较临床结局，CD 123高表达患者显示出良好的预后，与CD 123低表达和CD 123阴性患者相比，OS（p = 0.005）、EFS（p = 0.017）和RFS（p = 0.045）显著更好。随后在CCCG-ALL-2015队列中证实了CD 123表达的预后价值。单变量和多变量考克斯回归模型分析显示，在该队列中，CD 123高表达与有利的EFS独立相关（OR：0.528; 95% CI：0.327至0.853; p = 0.009）。在没有明确的肿瘤基因组异常的患者中，CD 123高表达强烈提示上级生存率，并且在两个队列中被确定为EFS和RFS的独立预后因素。一组B-ALL缺乏决定预后的基因组畸变，这对风险分层提出了挑战。我们的研究结果显示，白血病原始细胞高表达的CD 123与儿童B-ALL的良好临床结局相关，CD 123可作为一个有前途的预后预测因子，特别是在没有决定性遗传畸变的患者中。
Aberrant expression of CD123 (IL-3Rα) was observed in various hematological malignancies including acute lymphoblastic leukemia (ALL), which is the most common malignancy in childhood. Although widely used for minimal residual disease (MRD) monitoring, the prognostic value of CD123 has not been fully characterized in pediatric B-ALL. This retrospective study aims to evaluate the association between the CD123 expression of leukemic blasts and the outcomes of the pediatric B-ALL patients. A total of 976 pediatric B-ALL, including 328 treated with CCLG-ALL-2008 protocol and 648 treated with CCCG-ALL-2015 protocol, were recruited in this retrospective study. CD123 expression was evaluated by flow cytometry. Patients with >50, 20–50, or <20% of CD123 expressing blasts were grouped into CD123high, CD123low, and CD123neg, respectively. The correlation between CD123 expression and the patients’ clinical characteristics, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) were studied statistically. Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123high. In the CCLG-ALL-2008 cohort, CD123high was significantly associated with chromosome hyperdiploidy (p < 0.0001), risk stratification (p = 0.004), and high survival rate (p = 0.005). By comparing clinical outcomes, patients with CD123high displayed favorable prognosis, with a significantly better OS (p = 0.005), EFS (p = 0.017), and RFS (p = 0.045), as compared to patients with CD123low and CD123neg. The prognostic value of CD123 expression was subsequently confirmed in the CCCG-ALL-2015 cohort. Univariate and multivariate cox regression model analysis showed that high CD123 expression was independently associated with favorable EFS (OR: 0.528; 95% CI: 0.327 to 0.853; p = 0.009) in this cohort. In patients without prognosis-defining genomic abnormalities, high CD123 expression strongly indicated superior survival rates and was identified as an independent prognosis factor for EFS and RFS in both cohorts. A group of B-ALL lacks prognosis-defining genomic aberrations, which proposes a challenge in risk stratification. Our findings revealed that high CD123 expression of leukemic blasts was associated with favorable clinical outcomes in pediatric B-ALL and CD123 could serve as a promising prognosis predictor, especially in patients without prognosis-defining genetic aberrations.
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影响因子：
2.7
作者：
Liu, Jun;Tan, Xu;Zhang, Cheng
通讯作者：
Zhang, Cheng
影响因子：
12.8
作者：
Cui, Lei;Li, Zhi-Gang;Wu, Min-Yuan
通讯作者：
Wu, Min-Yuan
影响因子：
10.1
作者：
Angelova E;Audette C;Kovtun Y;Daver N;Wang SA;Pierce S;Konoplev SN;Khogeer H;Jorgensen JL;Konopleva M;Zweidler-McKay PA;Medeiros LJ;Kantarjian HM;Jabbour EJ;Khoury JD
通讯作者：
Khoury JD
DOI：
10.1182/asheducation-2012.1.389
发表时间：
2012-12-01
影响因子：
3
作者：
Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
DOI：
10.1016/j.beha.2020.101193
发表时间：
2020-09
期刊：
Best practice & research. Clinical haematology
影响因子：
--
作者：
Kimura S;Mullighan CG
通讯作者：
Mullighan CG