Congenital leukaemia after use of permethrin during pregnancy
Congenital leukaemia is a rare disease which affects about one child in 200 000–250 000 live births a year. In spite of its rarity, congenital leukaemia has stimulated much interest because of the opportunity to learn more about the underlying causes of in utero leukaemogenesis… Congenital and infant leukaemia are often associated with rearrangements of the MLL gene at chromosome 11q23.2 Several substances have been examined for their potential to cross the placental barrier and to induce such a chromosomal break at 11q23/MLL.3 4
Here we extend the list of drugs capable of cleaving the MLL gene, at least when cells are exposed in culture. Together with a rather unusual case history, our experimental data shed some light on the generation of congenital leukaemia and may help to prevent some of the fatal cases of this disease…
The mother had apparently suffered from arachnophobia since early childhood. Two years before her pregnancy she began to overuse aerosolised permethrin…. Permethrin is a widely used household insecticide providing protection from the malaria vector Anopheles.7 8 It is also known to be an efficacious drug against scabies and the head louse Pediculosis capitis.9 10 Compared with other drugs, it is considered safe and its topi- cal use is recommended even for neonates with scabies.11 However, it has been linked to the generation of both chromo- somal aberrations in bone marrow cells of mice and DNA lesions in human lymphocytes.12–14 We therefore hypothesised that permethrin crossed the placenta of the pregnant woman and affected the haematopoietic precursor cells in the developing fetus, resulting in leukaemogenesis. We therefore tried to generate the rearrangements within the MLL oncogene in vitro by exposing BV173 cells to 50 μM permeth- rin. After 24 hours of exposure, the permethrin treated BV173 cells showed a clear MLL rearrangement, whereas the untreated cells showed the wild type MLL gene only (fig 1B). Therefore we strongly recommend great caution in the use of permethrin during pregnancy. Even if definitive conclusions cannot be drawn from a single isolated case, our data strongly suggest that permethrin may have severe side effects when fetal haematopoietic precursor cells are exposed in utero. In the same vein, a recent report from a multinational collabora- tion indicated that use of mosquitocidal drugs during pregnancy is significantly associated with infant leukaemia.4 It is especially noteworthy that the authors found this associ- ation only for the MLL rearranged cases and not for MLL germline cases. This strongly argues against selection bias in their case-control study and supports the hypothesis that in utero exposure causes the MLL rearrangements.