Modulation of the Gene Fusion Prevalence in Newborns by Corticosteroid Use During Pregnancy.
Eduard Gratacós, Helena Castillo, Pablo Menéndez, Clara Bueno, Leticia Benítez, Ersen Kameri, Rosa Casas, Ramon Estruch, Eduard Vieta, Lina Youssef, Francesca Crovetto, Sara Castro-Barquero, Arndt Borkhardt, Ute Fischer, Fàtima Crispi, Roger Borras, Marta Larroya
Journal: International journal of molecular sciences
2025;26(7):
PMID: 40243620
Abstract
-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 and the generation of a preleukemic clone in utero. Secondary hits after birth are necessary to convert the preleukemic clone into clinically overt leukemia. However, prenatal factors triggering the first hit have not yet been determined. Here, we explore the influence of maternal factors during pregnancy on the prevalence of the fusion. To this end, we employed a nested interventional cohort study (IMPACT-BCN trial), including 1221 pregnancies (randomized into usual care, a Mediterranean diet, or mindfulness-based stress reduction) and determined the prevalence of the fusion gene in the DNA of cord blood samples at delivery ( = 741) using the state-of-the-art GIPFEL (genomic inverse PCR for exploration of ligated breakpoints) technique. A total of 6.5% ( = 48 of 741) of healthy newborns tested positive for . Our multiple regression analyses showed a trend toward lower prevalence in offspring of the high-adherence intervention groups. Strikingly, corticosteroid use for lung maturation during pregnancy was significantly associated with (adjusted OR 3.9, 95% CI 1.6-9.8) in 39 neonates, particularly 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 of developing + preleukemic clones and potentially leukemia after birth. Taken together, this study indicates that preleukemia prevalence may be modulated and potentially prevented.
Address:
BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.; Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.; German Cancer Consortium, Partner Site Essen-Düsseldorf, 40225 Düsseldorf, Germany.; Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.; BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Red Española de Terapias Avanzadas-Instituto de Salud Carlos III (ISCII), 28029 Madrid, Spain.; Centro de Investigación Biomédica en Red Cáncer(CIBER-ONC), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain.; BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain.; BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.; Josep Carreras Leukemia Research Institute, 08916 Barcelona, Spain.; Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.; Deutsches Krebsforschungszentrum (DKFZ), 69120 Heidelberg, Germany.; BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Josep Carreras Leukemia Research Institute, 08916 Barcelona, Spain.; Department of Biomedicine, School of Medicine, University of Barcelona, 08014 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, 28029 Madrid, Spain.; Institut de Recerca en Nutrició i Seguretat Alimentaria, University of Barcelona, 08014 Barcelona, Spain.; Department of Internal Medicine, Hospital Clinic, University of Barcelona, 08014 Barcelona, Spain.; Department of Internal Medicine, Hospital Clinic, University of Barcelona, 08014 Barcelona, Spain.; Centro de Investigación Biomédica en Red y Salud Mental, CIBERSAM, Instituto de Salud Carlos III, 28029 Madrid, Spain.; Department of Psychiatry and Psychology, Hospital Clinic, Neuroscience Institute, IDIBAPS, University of Barcelona, CIBERSAM, 08014 Barcelona, Spain.; Department of Biomedicine, School of Medicine, University of Barcelona, 08014 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, 28029 Madrid, Spain.; Department of Pediatric Oncology, Hematology and Clinical Immunology, University Children's Hospital, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.; German Cancer Consortium, Partner Site Essen-Düsseldorf, 40225 Düsseldorf, Germany.; BCNatal|Fetal Medicine Research Center, Hospital Clínic and Hospital Sant Joan de Deu, University of Barcelona, 08950 Barcelona, Spain.; Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain.; Institut de Recerca Sant Joan de Déu, 08950 Barcelona, Spain.
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MeSH Terms:
Humans,
Female,
Pregnancy,
Core Binding Factor Alpha 2 Subunit,
Infant, Newborn,
Oncogene Proteins, Fusion,
ETS Translocation Variant 6 Protein,
Proto-Oncogene Proteins c-ets,
Adrenal Cortex Hormones,
Repressor Proteins,
Male,
Adult,
Precursor Cell Lymphoblastic Leukemia-Lymphoma,
Prevalence
