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

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.

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies

“…This is supported by other studies, which have also shown that higher expression of SLC7A11, GPX4 and LPCAT3 is associated with a worse prognosis in AML, while overexpression of TFRC, which encodes the transferrin receptor, was found to protect cells against ferroptosis [113,114]. In children with non-M3 AML, FTH1 expression is associated with a poor prognosis and is upregulated during the proliferation of AML cell lines [115]. Numerous publications have identified other ferroptosis-related gene signatures, eluding to the relevance of ferroptosis in AML but also indicating the dataset used and other factors may contribute to what genes can be used to predict both prognosis and ferroptosis-sensitivity in AML [116][117][118][119][120][121].…”

Baicalin induces ferroptosis in oral squamous cell carcinoma by suppressing the activity of FTH1

“…12 In children with non-M3 acute myeloid leukemia, high levels of FTH1 have been shown to promote the proliferation and inhibit the ferroptosis of leukemia cells, suggesting that FTH1 is a risk factor and treatment target in non-M3 acute myeloid leukemia. 13 Furthermore, Mao et al have found that the level of ferroptosis gene FTH1 is significantly relevant to the survival of HNSCC samples, and Tanshinone IIA (TanIIA) is capable of inhibiting cell survival and the invasiveness of Fadu cells (a human hypopharynx squamous carcinoma cell line), via suppressing FTH1. 14 In contrast, interaction between FTH1 and PRDX6 in cancer cells results in a less invasive phenotype.…”