Modulation of the ETV6::RUNX1 gene fusion prevalence in newborns by corticosteroid use during pregnancy.

ETV6::RUNX1 positive pediatric acute lymphoblastic leukemia frequently has a prenatal origin and follows a two-hit model: a first somatic alteration leads to the formation of the oncogenic fusion gene ETV6::RUNX1 and the generation of a preleukemic clone in utero. S econdary hits after birth are necessary to convert the preleukemic clone into clinically overt leukemia. However, prenatal factors triggering the first hit are still not determined. Here, we explore the influence of maternal factors during pregnancy on the prevalence of the ETV6::RUNX1 fusion. To this end, we employed a nested interventional cohort study ( IMPACT-BCN trial ), including 1221 pregnancies (randomized into usual care, Mediterranean diet, or mindfulness-based stress reduction) and determined the prevalence of the fusion gene in DNA of cord blood samples at delivery (n=741) using the state-of-the-art GIPFEL ( genomic inverse PCR for exploration of ligated breakpoints) technique. 6.5% (n=48 of 741) of healthy newborns tested positive for ETV6::RUNX1. Our multiple regression analyses showed a trend towards lower ETV6::RUNX1 prevalence in offspring of the high-adherence intervention groups. Strikingly, corticosteroid use for lung maturation during pregnancy was significantly associated with ETV6::RUNX1 (adjusted OR 3.9, 95%CI 1.6-9.8) in 39 neonates, in particular if applied before 26 weeks of gestation (OR 7.7, 95%CI 1.08-50) or if betamethasone (OR 4.0, 95%CI 1.4-11.3) was used. Prenatal exposure to corticosteroids within a critical time window may therefore increase the risk to develop ETV6::RUNX1+ preleukemic clones and potentially leukemia after birth. Taken together, this study indicates that ETV6::RUNX1 preleukemia prevalence may be modulated and potentially prevented. Supplementary Material File (manuscript clean.docx) - Download - 175.43 KB Information & Authors Information Version history Peer review timeline Published International Journal of Molecular Sciences Version of Record25 Mar 2025Published Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 312views 215downloads Citations Download citation Leticia Benítez, Ute Fischer, Fàtima Crispi, et al. Modulation of the ETV6::RUNX1 gene fusion prevalence in newborns by corticosteroid use during pregnancy.. Authorea. 23 January 2025. DOI: https://doi.org/10.22541/au.173762133.34481154/v1 DOI: https://doi.org/10.22541/au.173762133.34481154/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu. Cited by - Special Issue “Molecular Insights into the Developmental Origins of Health and Disease”, International Journal of Molecular Sciences, 26, 23, (11579), (2025).https://doi.org/10.3390/ijms262311579 Loading...