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Bioelectromagnetics. 2019 Jul;40(5):343-353. doi: 10.1002/bem.22193. Epub 2019 Jun 3.

Novel ETV6-RUNX1 Mouse Model to Study the Role of ELF-MF in Childhood B-Acute Lymphoblastic Leukemia: a Pilot Study.

Author information

1
Department of Cell Biology and Immunology, Centro de Biologia Molecular Severo Ochoa (CBMSO), CSIC/UAM, Madrid, Spain.
2
Cancer Research Unit, Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain.
3
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/Universidad de Salamanca, Salamanca, Spain.
4
IT'IS Foundation, Zurich, Switzerland.
5
Department of Information Technology and Electrical Engineering, ETHZ, Zurich, Switzerland.
6
Fraunhofer ITEM, Toxicology and Environmental Hygiene, Hannover, Germany.

Abstract

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.

KEYWORDS:

ARIMMORA project; cancer susceptibility; exposure; magnetic field

PMID:
31157932
DOI:
10.1002/bem.22193

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