Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome.
Oxidative stress leads to increased mutation frequency in a murine model of myelodysplastic syndrome.
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DOI：
10.1016/j.leukres.2013.07.008
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发表时间：
2014-01
影响因子：
2.7
通讯作者：
Aplan PD
中科院分区：
文献类型：
--
作者：
Chung YJ;Robert C;Gough SM;Rassool FV;Aplan PD
骨髓增生异常综合征(MDS)的特征是无效的造血、不典型增生和向急性髓系白血病(AML)的转化。虽然有人认为额外的突变会导致MDS进展为AML，但这些突变的致病因素(S)仍不清楚。氧化应激是一个潜在的原因，因此，我们评估了NUP98-Hoxd13(NHD13)转基因小鼠的ROS水平，这是一种MDS的小鼠模型。在表达细胞增殖标志CD71的骨髓有核细胞(BMNC)以及来自NHD13小鼠的未成熟、谱系阴性的骨髓有核细胞中检测到ROS水平升高。在NHD13 BMNC中，除了ROS增加外，DNA双链断裂和G2/M期细胞周期检查点的激活也被观察到。最后，使用体内突变频率检测，我们检测到NHD13 BMNC的突变频率增加。这些结果表明，氧化应激可能通过DNA损伤的无效修复和获得致癌突变来促进MDS到AML的疾病进展。
The myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it has been suggested that additional mutations lead to progression of MDS to AML, the causative agent(s) for such mutations remains unclear. Oxidative stress is a potential cause, therefore, we evaluated levels of reactive oxygen species (ROS) in NUP98-HOXD13 (NHD13) transgenic mice, a murine model for MDS. Increased levels of ROS were detected in bone marrow nucleated cells (BMNC) that express CD71, a marker for cell proliferation, as well as immature, lineage negative bone marrow nucleated cells from NHD13 mice. In addition to the increase in ROS, increased DNA double strand breaks and activation of a G2/M phase cell cycle checkpoint were noted in NHD13 BMNC. Finally, using an in vivo assay for mutation frequency, we detected an increased mutation frequency in NHD13 BMNC. These results suggest that oxidative stress may contribute to disease progression of MDS to AML through ineffective repair of DNA damage and acquisition of oncogenic mutations.
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影响因子：
3.1
作者：
Ghoti, Hussam;Amer, Johnny;Fibach, Eitan
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DOI：
10.1073/pnas.0409130102
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作者：
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