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

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

doi:10.3389/fonc.2021.783114

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.

Highlights

The t(8;21)(q22;q22) is the most commonly observed chromosomal translocation in acute myeloid leukemia (AML) patients; it generates the AML1-ETO (AE) fusion protein [1–4]
It was concluded that Chinese AML1ETO patients had many coexisting gene mutations, and the interaction was very complicated
We explored the structural characteristics of AML1-ETO of each patient by next-generation sequencing (NGS) platform and found that the number of C-kit had significant effects on prognosis

Summary

Introduction

The t(8;21)(q22;q22) is the most commonly observed chromosomal translocation in acute myeloid leukemia (AML) patients; it generates the AML1-ETO (AE) fusion protein [1–4]. The median age of these patients is considerably lower, and the prognosis is better compared to normal-karyotype AMLs or other chromosome aberrations. This favorable consequence is associated with a higher complete remission (CR) rate and lower relapse incidence [8–10]. Some subtypes of AML1-ETO-postive AML patients were observed with a higher incidence of relapse and poorer outcomes, and the coexisting c-kit activation mutations may be one of the underlying reasons. Adult patients with CBF leukemia had 12.8%–46.1% of c-kit mutations [11–13]. For example, if oncogene mutations such as ASXL2,

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