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

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...

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Autores principales: Zhang, Junlin, Liu, Liying, Wei, Jinshuang, Wu, Xiaojing, Luo, Jianming, Wei, Hongying, Ning, Liao, He, Yunyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928996/
https://www.ncbi.nlm.nih.gov/pubmed/36818670
http://dx.doi.org/10.3389/fonc.2022.1068094
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author Zhang, Junlin
Liu, Liying
Wei, Jinshuang
Wu, Xiaojing
Luo, Jianming
Wei, Hongying
Ning, Liao
He, Yunyan
author_facet Zhang, Junlin
Liu, Liying
Wei, Jinshuang
Wu, Xiaojing
Luo, Jianming
Wei, Hongying
Ning, Liao
He, Yunyan
author_sort Zhang, Junlin
collection PubMed
description 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.
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spelling pubmed-99289962023-02-16 High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia Zhang, Junlin Liu, Liying Wei, Jinshuang Wu, Xiaojing Luo, Jianming Wei, Hongying Ning, Liao He, Yunyan Front Oncol Oncology 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. Frontiers Media S.A. 2023-02-01 /pmc/articles/PMC9928996/ /pubmed/36818670 http://dx.doi.org/10.3389/fonc.2022.1068094 Text en Copyright © 2023 Zhang, Liu, Wei, Wu, Luo, Wei, Ning and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Junlin
Liu, Liying
Wei, Jinshuang
Wu, Xiaojing
Luo, Jianming
Wei, Hongying
Ning, Liao
He, Yunyan
High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title_full High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title_fullStr High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title_full_unstemmed High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title_short High expression level of the FTH1 gene is associated with poor prognosis in children with non-M3 acute myeloid leukemia
title_sort high expression level of the fth1 gene is associated with poor prognosis in children with non-m3 acute myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928996/
https://www.ncbi.nlm.nih.gov/pubmed/36818670
http://dx.doi.org/10.3389/fonc.2022.1068094
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