Research Paper|Volume 15, Issue 22|pp 13486—13503

The ferroptosis landscape in acute myeloid leukemia

Zhixin Ma¹, Wenle Ye², Xin Huang², Xia Li², Fenglin Li², Xiangjie Lin², Chao Hu², Jinghan Wang², Jie Jin², Bo Zhu¹, Jiansong Huang²

¹Clinical Prenatal Diagnosis Center, Key Laboratory of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
²Department of Hematology, Key Laboratory of Hematologic Malignancies, Diagnosis and Treatment, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

Received: June 2, 2021Accepted: October 17, 2023Published: November 29, 2023

https://doi.org/10.18632/aging.205257

Copyright: © 2023 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Ferroptosis induction through the suppression of glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2) has proven to be an effective approach in eliminating chemotherapy-resistant cells of various types. However, a comprehensive understanding of the roles of GPX4 and AIFM2 in acute myeloid leukemia (AML) has not yet been achieved. Using cBioPortal, DepMap, GEPIA, Metascape, and ONCOMINE, we compared the transcriptional expression, survival data, gene mutation, methylation, and network analyses of GPX4- and AIFM2-associated signaling pathways in AML. The results revealed that high expression levels of GPX4 and AIFM2 are associated with an adverse prognosis for AML patients. Overexpression of AIFM2 correlated with elevated mutation frequencies in NPM1 and DNMT3A. GPX4 upregulation modulated the following pathways: GO:0045333, cellular respiration; R-HSA-5389840, mitochondrial translation elongation; GO:0009060, aerobic respiration; R-HSA-9609507, protein localization; and R-HSA-8953854, metabolism of RNA. On the other hand, the overexpression of AIFM2 influenced the following processes: GO:0048704, embryonic skeletal system morphogenesis; GO:0021546, rhombomere development; GO:0009954, proximal/distal pattern formation; and GO:0048732, gland development. This study identifies the high expression of GPX4 and AIFM2 as novel biomarkers predicting a poor prognosis for AML patients. Furthermore, ferroptosis induction may improve the stratified treatment of AML.