EP06.08: Influence of prenatal risk factors on the prevalence of preleukemic ETV6: RUNX1 lesions in cord blood

Half of cases of childhood leukemia start during fetal life with the formation of preleukemic clones in utero. This study aimed to explore the influence of prenatal risk factors on the prevalence of preleukemic ETV6:RUNX1 fusion gene on cord blood samples. A nested cohort study including cord blood samples from the IMPACT-BCN trial (2017-2020), including 1221 pregnancies randomised to three interventions: usual care, Mediterranean diet, or stress reduction. Available cord blood samples collected at delivery were analysed using a Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL) to check the neonatal ETV6:RUNX1 positivity (n = 741). Multiple regression analyses were used to determine the association of maternal and prenatal characteristics with neonatal ETV6: positivity. Among 741 available cord blood samples, the prevalence of neonatal ETV6:RUNX1 was 6.5% with no significant association with maternal lifestyle interventions. In a multiple logistic regression analysis, maternal Maghreb ethnicity (adjusted OR 10.5, 95% CI 2.4-45.4) and exogenous corticosteroid use during pregnancy (adjusted OR 3.9, 95% CI 1.6-9.8) were significantly associated with the appearance of neonatal ETV6:RUNX1 fusion gene. A higher probability was observed in those participants receiving the corticosteroids before 26 weeks of gestation (OR 7.7, 95% CI 1.08-50). This study identifies maternal Maghreb ethnicity and prenatal exposure to corticosteroids as potential risk factors for preleukemic lesions in offspring. Future studies are warranted to confirm these findings and design new prevention strategies.