Modulation of the ETV6::RUNX1 Gene Fusion Prevalence in Newborns by Corticosteroid Use During Pregnancy
Year: 2025
Type: article
Abstract: 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.
DOI: 10.3390/ijms26072971
Institutions: Hospital Sant Joan de Déu Barcelona, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung, Heinrich Heine University Düsseldorf, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red de Cáncer, Institut de Recerca Sant Joan de Déu, Josep Carreras Leukaemia Research Institute, Institució Catalana de Recerca i Estudis Avançats, Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, Centro de Investigación Biomédica en Red de Salud Mental
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: Impacto del crecimiento intrauterino restringido sobre el desarrollo pulmonar, G1255292432, G1341303, G1461523045, G1491211482, G1548510038, G1592438829, G195927840, G2036846235, G2054348530, G2119518415, G2329980862, G2501746636, G2646948029, G2682480861, G2756433129, G2866899207, G2867535091, G2929421261, G3103957572, G3122787131, G3177630868, G3404371184, G3469195297, G3538395869, G355572793, G3716565774, G3780745508, G3817536483, G3827577893, G3847058362, G3861374258, G3903708587, G3907071644, G3914624991, G3951775385, G4037294754, G4045982589, G4518921262, G4531780717, G4571183183, G4600584165, G4694973061, G4722345748, G4728921213, EDI-4-ALL - Frühe Erkennung und Intervention der akuten lymphatischen Leukämie im Kindesalter, Standort: Heinrich-Heine-Universität Düsseldorf, G4834040602, G4900950432, G5023238755, G51085903, G5128430132, G5165837919, G5345787338, G5490735505, G6005823474, G6078222917, G6086261655, G6115719638, G6117820179, G6122547664, G6153134307, G617399438, Identifizierung von Risikofaktoren und Ableitung von Signalwegabhängigkeiten für ETV6RUNX1+ Präleukämie, G6194251481, G6348400817, G6365058345, G6386557946, G6423921831, G6586503077, G666072902, G6832566931, G6980404552, G7047970265, G7110367544, G7188079284, G7194432091, G7298798089, G7327720778, G7368046947, G7368692467, G7384753141, G7393274827, G7409007238, G7409652322, G7495396186, G7675917524, G7881225964, G7924490226, G8046954393, G8048695341, G8123182514, G8143591470, G8175396361, G8395475425, G854264376, G8613684700, G8664522487, G8668909676, G891781936
OpenAlex ID: W4408807922