AUTHOR=Zheng Yongzhi , Huang Yan , Le Shaohua , Zheng Hao , Hua Xueling , Chen Zaisheng , Feng Xiaoqin , Li Chunfu , Zheng Mincui , Xu Honggui , He Yingyi , He Xiangling , Li Jian , Hu Jianda 

TITLE=High EVI1 Expression Predicts Adverse Outcomes in Children With De Novo Acute Myeloid Leukemia

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.712747

DOI=10.3389/fonc.2021.712747

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>A high ecotropic viral integration site 1 (<italic>EVI1)</italic> expression (<italic>EVI1</italic><sup>high</sup>) is an independent prognostic factor in adult acute myeloid leukemia (AML). However, little is known of the prognostic value of <italic>EVI1</italic><sup>high</sup> in pediatric AML. This study aimed to examine the biological and prognostic significance of <italic>EVI1</italic><sup>high</sup> in uniformly treated pediatric patients with AML from a large cohort of seven centers in China.</p></sec><sec><title>Methods</title><p>A diagnostic assay was developed to determine the relative <italic>EVI1</italic> expression using a single real-time quantitative polymerase chain reaction in 421 newly diagnosed pediatric AML patients younger than 14 years from seven centers in southern China. All patients were treated with a uniform protocol, but only 383 patients were evaluated for their treatment response. The survival data were included in the subsequent analysis (n = 35 for <italic>EVI1</italic><sup>high</sup>, n = 348 for <italic>EVI1</italic><sup>low</sup>).</p></sec><sec><title>Results</title><p><italic>EVI1</italic><sup>high</sup> was found in 9.0% of all 421 pediatric patients with <italic>de novo</italic> AML. <italic>EVI1</italic><sup>high</sup> was predominantly found in acute megakaryoblastic leukemia (FAB M7), <italic>MLL</italic> rearrangements, and unfavorable cytogenetic aberrance, whereas it was mutually exclusive with t (8; 21), inv (16)/t (16; 16), <italic>CEBPA</italic>, <italic>NPM1</italic>, or <italic>C-KIT</italic> mutations. In the univariate Cox regression analysis, <italic>EVI1</italic><sup>high</sup> had a significantly adverse 5-year event-free survival (EFS) and overall survival (OS) [hazard ratio (HR) = 1.821 and 2.401, <italic>p</italic> = 0.036 and 0.005, respectively]. In the multivariate Cox regression analysis, <italic>EVI1</italic><sup>high</sup> was an independent prognostic factor for the OS (HR = 2.447, <italic>p</italic> = 0.015) but not EFS (HR = 1.556, p = 0.174). Furthermore, <italic>EVI1</italic><sup>high</sup> was an independent adverse predictor of the OS and EFS of patients with <italic>MLL</italic> rearrangements (univariate analysis: HR = 9.921 and 7.253, both <italic>p</italic> &lt; 0.001; multivariate analysis: HR = 7.186 and 7.315, <italic>p</italic> = 0.005 and 0.001, respectively). Hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) provided <italic>EVI1</italic><sup>high</sup> patients with a tendential survival benefit when compared with chemotherapy as a consolidation (5-year EFS: 68.4% <italic>vs.</italic> 50.8%, <italic>p</italic> = 0.26; 5-year OS: 65.9% <italic>vs.</italic> 54.8%, <italic>p</italic> = 0.45).</p></sec><sec><title>Conclusion</title><p>It could be concluded that <italic>EVI1</italic><sup>high</sup> can be detected in approximately 10% of pediatric AML cases. It is predominantly present in unfavorable cytogenetic subtypes and predicts adverse outcomes. Whether pediatric patients with <italic>EVI1</italic><sup>high</sup> AML can benefit from HSCT in CR1 needs to be researched further.</p></sec>