Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS
Iron overload promotes the progression of MLL-AF9 induced acute myeloid leukemia by upregulation of FOS
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DOI：
10.1016/j.canlet.2024.216652
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发表时间：
2024-02-01
期刊：
影响因子：
9.7
通讯作者：
Zhang，Xuezhong
中科院分区：
文献类型：
--
作者：
Yang，Feifei;Cui，Xiaoxi;Zhang，Xuezhong
系统性铁超载是急性髓细胞白血病（AML）患者常见的临床挑战，导致严重并发症，影响患者的生活质量和总生存期。临床应用铁螯合治疗后症状可缓解。然而，铁超载在白血病发生和发展中的作用和机制仍不清楚。本研究采用MLL-AF 9诱导的急性髓系白血病（AML）小鼠模型和裸鼠移植瘤模型，研究了铁超载与AML临床结局的相关性，并进一步探讨了铁超载在AML中的作用和病理生理机制。AML患者的铁蛋白水平升高，特别是在粒单核细胞（M4）或单核细胞（M5）亚型中。高水平的铁表达与AML患者的预后恶化和AML小鼠的生存时间缩短相关。此外，铁超载通过上调FOS促进白血病细胞增殖，从而增加骨髓（BM）和髓外组织中的肿瘤负荷。总的来说，我们的研究结果为铁超载在AML中的作用提供了新的见解。此外，这项研究可能提供一个潜在的治疗目标，以改善AML患者的结果和铁螯合治疗AML的前瞻性评价的理由。
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 ofFOS. 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.