High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations

Zhiheng Li; Xinran Chu; Li Gao; Jing Ling; Peifang Xiao; Jun Lu; Yi Wang; Hailong He; Jianqin Li; Yixin Hu; Jie Li; Jian Pan; Sheng Xiao; Shaoyan Hu

doi:10.3389/fonc.2021.614420

High Expression of Interleukin-3 Receptor Alpha Chain (CD123) Predicts Favorable Outcome in Pediatric B-Cell Acute Lymphoblastic Leukemia Lacking Prognosis-Defining Genomic Aberrations

Front Oncol. 2021 Mar 16:11:614420. doi: 10.3389/fonc.2021.614420. eCollection 2021.

Authors

Zhiheng Li^{1

2

3}, Xinran Chu³, Li Gao³, Jing Ling³, Peifang Xiao³, Jun Lu³, Yi Wang³, Hailong He³, Jianqin Li³, Yixin Hu³, Jie Li³, Jian Pan¹, Sheng Xiao², Shaoyan Hu³

Affiliations

¹ Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, China.
² Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States.
³ Department of Hematology, Children's Hospital of Soochow University, Suzhou, China.

Abstract

Background: 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.

Methods: 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 CD123^high, CD123^low, and CD123^neg, 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.

Results: Of 976 pediatric B-ALL, 53.4% from the CCLG-ALL-2008 cohort and 49.2% from the CCCG-ALL-2015 cohort were CD123^high. In the CCLG-ALL-2008 cohort, CD123^high 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 CD123^high 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 CD123^low and CD123^neg. 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.

Conclusions: 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.

Keywords: B-cell acute lymphoblastic leukemia; CD123; favorable; pediatric; prognosis.