High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

Junlin Zhang; Liying Liu; Jinshuang Wei; Xiaojing Wu; Jianming Luo; Hongying Wei; Liao Ning; Yunyan He

doi:10.3389/fonc.2022.1068094

High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia

Front Oncol. 2023 Feb 1:12:1068094. doi: 10.3389/fonc.2022.1068094. eCollection 2022.

Authors

Junlin Zhang¹, Liying Liu¹, Jinshuang Wei¹, Xiaojing Wu¹, Jianming Luo^{1

2}, Hongying Wei¹, Liao Ning^{1

2

3}, Yunyan He^{1

2

3}

Affiliations

¹ First Affiliated Hospital of Guangxi Medical University, Nanning, China.
² The Key Laboratory of Children's Disease Research in Guangxi's Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region, Nanning, China.
³ The Affiliated Children's Hospital of Suzhou University, Suzhou, Jiangsu, China.

Abstract

Acute myelogenous leukemia (AML) is a disease that severely affects the physical health of children. Thus, we aimed to identify biomarkers associated with AML prognosis in children. Using transcriptomics on an mRNA dataset from 27 children with non-M3 AML, we selected genes from among those with the top 5000 median absolute deviation (MAD) values for subsequent analysis which showed that two modules were associated with AML risk groups. Thus, enrichment analysis was performed using genes from these modules. A one-way Cox analysis was performed on a dataset of 149 non-M3 AML patients downloaded from the TCGA. This identified four genes as significant: FTH1, RCC2, ABHD17B, and IRAK1. Through survival analysis, FTH1 was identified as a key gene associated with AML prognosis. We verified the proliferative and regulatory effects of ferroptosis on MOLM-13 and THP-1 cells using Liproxstatin-1 and Erastin respectively by CCK-8 and flow cytometry assays. Furthermore, we assayed expression levels of FTH1 in MOLM-13 and THP-1 cells after induction and inhibition of ferroptosis by real-time quantitative PCR, which showed that upregulated FTH1 expression promoted proliferation and inhibited apoptosis in leukemia cells. In conclusion, high expression of FTH1 promoted proliferation and inhibited apoptosis of leukemic cells through the ferroptosis pathway and is thus a potential risk factor that affects the prognosis of non-M3 AML in children.

Keywords: AML; FTH1; WGCNA; ferroptosis; prognosis.