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

Elena Campos-Sanchez, Carolina Vicente-Dueñas, Guillermo Rodríguez-Hernández, Myles Capstick, Niels Kuster, Clemens Dasenbrock, Isidro Sánchez-García, and César Cobaleda, Bioelectromagnetics, Volume 40, Issue 5, July 2019, pp. 343–353, online 3 June 2019; doi: 10.1002/bem.22193

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, however, was compromised by a lack of an appropriate animal model that recapitulates the natural history of this disease. Childhood B-cell acute lymphoblastic leukemia (B-ALL) results from 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 via origination of a pre-leukemic clone that requires secondary hits for full-blown disease to appear. To develop potential prophylactic interventions, we need to identify environmental triggers that constitute the second hit. Recently, we generated a B-ALL mouse model of the human ETV6-RUNX1⁺ pre-leukemic 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 animals did. Although the results are statistically non-significant due to the limited number of mice used in this pilot experiment, the results show, overall, that the newly developed Sca1-ETV6-RUNX1 mouse can be successfully used for ELF-MF exposure studies about the etiology of childhood B-ALL.

The scientific and technical impact of the study can be summarized as:

• An exposure system designed and fabricated by the IT'IS Foundation was used to expose a group of 34 transgenic Sca1‐ETV6‐RUNX1 mice to 50 Hz MF at 1.5 mT from conception until 3 months of age
• The mice were monitored from birth until 2 years of age, and a small but statistically significant transient decrease in the numbers of CD8⁺ T‐cells in the peripheral blood was observed in exposed mice at 60 days post-partum
• The overall survival rate of exposed mice was similar to that of unexposed mice for up to 24 months; of 8 exposed transgenic mice that died during the course of the experiment, 1 was found to have developed B-ALL
• The Sca1‐ETV6‐RUNX1 mouse model is a promising animal model for for the investigation of childhood B‐ALL that provides, for the first time, an in vivo tool for probing the epidemiologically observed association of childhood leukemia with ELF‐MF exposure

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