Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS

• Published in: Cancer letters 2024-02, Vol.583, p.216652-216652, Article 216652
• Main Authors: Yang, Feifei, Cui, Xiaoxi, Wang, Hao, Zhang, Dongyue, Luo, Shulin, Li, Yifei, Dai, Yibo, Yang, Dan, Zhang, Xiuqun, Wang, Lina, Zheng, Guoguang, Zhang, Xuezhong
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; FOS; Iron overload; Leukemia progression
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2024.216652

Systemic iron overload is a common clinical challenge leading to significantly serious complications in patients with acute myeloid leukemia (AML), which affects both the quality of life and the overall survival of patients. Symptoms can be relieved after iron chelation therapy in clinical practice. However, the roles and mechanisms of iron overload on the initiation and progression of leukemia remain elusive. Here we studied the correlation between iron overload and AML clinical outcome, and further explored the role and pathophysiologic mechanism of iron overload in AML by using two mouse models: an iron overload MLL-AF9-induced AML mouse model and a nude xenograft mouse model. Patients with AML had an increased ferritin level, particularly in the myelomonocytic (M4) or monocytic (M5) subtypes. High level of iron expression correlated with a worsened prognosis in AML patients and a shortened survival time in AML mice. Furthermore, iron overload increased the tumor load in the bone marrow (BM) and extramedullary tissues by promoting the proliferation of leukemia cells through the upregulation of FOS. Collectively, our findings provide new insights into the roles of iron overload in AML. Additionally, this study may provide a potential therapeutic target to improve the outcome of AML patients and a rationale for the prospective evaluation of iron chelation therapy in AML. •AML patients had an increased ferritin level, particularly in the M4 or M5 subtypes.•Iron overload correlated with a worsened prognosis in AML patients and a shortened survival time in AML mice.•Iron overload increased the tumor load in the BM and extramedullary tissues.•Iron overload promoted the proliferation of leukemia cells through the upregulation of FOS.