A Predictor Combining Clinical and Genetic Factors for AML1-ETO Leukemia Patients

Min Yang; Bide Zhao; Jinghan Wang; Yi Zhang; Chao Hu; Lixia Liu; Jiayue Qin; Feng Lou; Shanbo Cao; Chengcheng Wang; Wenjuan Yu; Hongyan Tong; Haitao Meng; Jian Huang; Honghu Zhu; Jie Jin

doi:10.3389/fonc.2021.783114

A Predictor Combining Clinical and Genetic Factors for AML1-ETO Leukemia Patients

Front Oncol. 2022 Jan 14:11:783114. doi: 10.3389/fonc.2021.783114. eCollection 2021.

Authors

Min Yang^{1

2

3}, Bide Zhao⁴, Jinghan Wang^{1

2

3}, Yi Zhang^{1

2

3}, Chao Hu^{1

2

3}, Lixia Liu⁵, Jiayue Qin⁵, Feng Lou⁵, Shanbo Cao⁵, Chengcheng Wang⁵, Wenjuan Yu^{1

2

3}, Hongyan Tong^{1

2

3}, Haitao Meng^{1

2

3}, Jian Huang^{1

2

3}, Honghu Zhu^{1

2

3}, Jie Jin^{1

2

3}

Affiliations

¹ Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Institute of Hematology, Zhejiang University, Hangzhou, China.
³ Zhejiang Province Key Laboratory of Hematology Oncology Diagnosis and Treatment, Hangzhou, China.
⁴ Department of Hematology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁵ Acornmed Biotechnology Co., Ltd., Beijing, China.

Abstract

Core Binding Factor (CBF)-AML is one of the most common somatic mutations in acute myeloid leukemia (AML). t(8;21)/AML1-ETO-positive acute myeloid leukemia accounts for 5-10% of all AMLs. In this study, we consecutively included 254 AML1-ETO patients diagnosed and treated at our institute from December 2009 to March 2020, and evaluated molecular mutations by 185-gene NGS platform to explore genetic co-occurrences with clinical outcomes. Our results showed that high KIT VAF(≥15%) correlated with shortened overall survival compared to other cases with no KIT mutation (3-year OS rate 26.6% vs 59.0% vs 69.6%, HR 1.50, 95%CI 0.78-2.89, P=0.0005). However, no difference was found in patients' OS whether they have KIT mutation in two or three sites. Additionally, we constructed a risk model by combining clinical and molecular factors; this model was validated in other independent cohorts. In summary, our study showed that c-kit other than any other mutations would influence the OS in AML1-ETO patients. A proposed predictor combining both clinical and genetic factors is applicable to prognostic prediction in AML1-ETO patients.

Keywords: AML-ETO; LASSO Cox regression; acute myeloid leukemia; next-generation sequencing; prognosis.