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Novel ETV6-RUNX1 Mouse Model to Study the Role of ELF-MF in Childhood B-Acute Lymphoblastic Leukemia: a Pilot Study.
Bioelectromagnetics ( IF 1.8 ) Pub Date : 2019-06-03 , DOI: 10.1002/bem.22193
Elena Campos-Sanchez 1 , Carolina Vicente-Dueñas 2 , Guillermo Rodríguez-Hernández 2, 3 , Myles Capstick 4 , Niels Kuster 4, 5 , Clemens Dasenbrock 6 , Isidro Sánchez-García 2, 3 , César Cobaleda 1
Affiliation  

Exposure to extremely low-frequency magnetic fields (ELF-MFs) has been classified by the International Agency for Research on Cancer (IARC) as "possibly carcinogenic to humans," based on limited scientific evidence concerning childhood leukemia. This assessment emphasized the lack of appropriate animal models recapitulating the natural history of this disease. Childhood B-cell acute lymphoblastic leukemia (B-ALL) is the result of complex interactions between genetic susceptibility and exposure to exogenous agents. The most common chromosomal alteration is the ETV6-RUNX1 fusion gene, which confers a low risk of developing the malignancy by originating a preleukemic clone requiring secondary hits for full-blown disease to appear. To develop potential prophylactic interventions, we need to identify the environmental triggers of the second hit. Recently, we generated a B-ALL mouse model of the human ETV6-RUNX1+ preleukemic state. Here, we present the results from the ARIMMORA pilot study, obtained by exposing 34 Sca1-ETV6-RUNX1 mice (vs. 27 unexposed) to a 50 Hz magnetic field of 1.5 mT with both fundamental and harmonic content, with an on/off cycle of 10 min/5 min, for 20 h/day, from conception until 3 months of age. Mice were monitored until 2 years of age and peripheral blood was periodically analyzed by flow cytometry. One of the exposed mice developed B-ALL while none of the non-exposed did. Although the results are statistically non-significant due to the limited number of mice used in this pilot experiment, overall, the results show that the newly developed Sca1-ETV6-RUNX1 mouse can be successfully used for ELF-MF exposure studies about the etiology of childhood B-ALL. Bioelectromagnetics. 2019;40:343-353. © 2019 Bioelectromagnetics Society.

中文翻译:


用于研究 ELF-MF 在儿童 B 急性淋巴细胞白血病中的作用的新型 ETV6-RUNX1 小鼠模型:一项试点研究。



根据有关儿童白血病的有限科学证据,国际癌症研究机构 (IARC) 将暴露于极低频磁场 (ELF-MF) 归类为“可能对人类致癌”。该评估强调缺乏适当的动物模型来概括这种疾病的自然史。儿童 B 细胞急性淋巴细胞白血病 (B-ALL) 是遗传易感性与外源性物质暴露之间复杂相互作用的结果。最常见的染色体改变是 ETV6-RUNX1 融合基因,该基因通过产生需要二次攻击才能出现全面疾病的白血病前期克隆,从而降低患恶性肿瘤的风险。为了制定潜在的预防干预措施,我们需要确定第二次打击的环境触发因素。最近,我们生成了人类 ETV6-RUNX1+ 白血病前期状态的 B-ALL 小鼠模型。在这里,我们展示了 ARIMMORA 试点研究的结果,该结果是通过将 34 只 Sca1-ETV6-RUNX1 小鼠(相对于 27 只未暴露)暴露于 1.5 mT 的 50 Hz 磁场(包含基波和谐波含量)并具有开/关周期而获得的从受孕到 3 个月大,每次 10 分钟/5 分钟,每天 20 小时。对小鼠进行监测直至2岁,并通过流式细胞术定期分析外周血。其中一只暴露的小鼠患上了B-ALL,而未暴露的小鼠则没有。尽管由于本次试验中使用的小鼠数量有限,结果在统计上不显着,但总体而言,结果表明新开发的 Sca1-ETV6-RUNX1 小鼠可以成功用于有关 ELF-MF 病因学的暴露研究童年B-ALL。生物电磁学。 2019;40:343-353。 © 2019 生物电磁学会。
更新日期:2019-06-03
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