RUNX1/ETO 通过 FLT3 和 RAC1 调节 t(8,21) 急性髓系白血病中的活性氧（ROS）水平。
RUNX1/ETO regulates reactive oxygen species (ROS) levels in t(8,21) acute myeloid leukaemia via FLT3 and RAC1.
机构信息
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Malaysia.
Faculty of Medicine, Lincoln University College, Petaling Jaya, Malaysia.
出版信息
Med Oncol. 2023 Jun 21;40(7):208. doi: 10.1007/s12032-023-02075-w.
Reactive oxygen species (ROS) homeostasis is crucial for leukaemogenesisand deregulation would hamper leukaemic progression. Although the regulatory effects of RUNX1/ETO has been extensively studied, its underlying molecular mechanims in ROS production in t(8,21) AML is yet to be fully elucidated. Here, we report that RUNX1/ETO could directly control FLT3 by occupying several DNA elements on FLT3 locus. The possible hijacking mechanism by RUNX1/ETO over FLT3 mediated ROS modulation in AML t(8;21) was made apparent when suppression of RUNX1/ETO led to decrement in ROS levels and the direct oxidative marker FOXO3 but not in FLT3 and RAC1 suppressed t(8,21) AML cell line Furthermore, nuclear import of RUNX1/ETO was aberrated following RUNX1/ETO and RAC1 suppression suggesting association in ROS control. A different picture was depicted in non t(8;21) cells where suppression of RAC1 and FLT3 led to decreased levels of FOXO3a and ROS. Results alltogether indicate a possible dysregulation of ROS levels by RUNX1/ETO in t(8,21) AML.
活性氧（ROS）稳态对于白血病的发生至关重要，其失调会阻碍白血病的进展。虽然 RUNX1/ETO 的调节作用已被广泛研究，但它在 t（8,21）AML 中产生 ROS 的潜在分子机制尚未完全阐明。在这里，我们报告 RUNX1/ETO 可以通过占据 FLT3 基因座上的几个 DNA 元件来直接控制 FLT3。当抑制 RUNX1/ETO 导致 ROS 水平和直接氧化标记 FOXO3 下降，但不影响 FLT3 和 RAC1 时，RUNX1/ETO 对 AML t（8;21）中 FLT3 介导的 ROS 调节的可能劫持机制变得明显抑制 t（8,21）AML 细胞系。此外，RUNX1/ETO 和 RAC1 抑制后 RUNX1/ETO 的核内输入异常，表明在 ROS 控制方面存在关联。在非 t（8;21）细胞中描绘了一幅不同的画面，其中 RAC1 和 FLT3 的抑制导致 FOXO3a 和 ROS 水平降低。结果表明，RUNX1/ETO 在 t（8,21）AML 中可能导致 ROS 水平的失调。
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