 have reported evidence that epigenetic differences measurable at birth are associated with later development of childhood acute lymphoblastic leukemia (ALL).){kind=link}
Investigators from Children’s Hospital Los Angeles (CHLA) have reported evidence that epigenetic differences measurable at birth are associated with later development of childhood acute lymphoblastic leukemia (ALL). In what is described as the largest population-based neonatal epigenetic analysis conducted in pediatric leukemia to date, the team identified distinct DNA methylation signatures in archived newborn blood specimens from patients who were subsequently diagnosed with ALL.
The findings were presented on December 6, 2025, in an oral session at the American Society of Hematology (ASH) Annual Meeting by Eric Nickels, MD, MS, pediatric oncologist at CHLA’s Cancer and Blood Disease Institute, in collaboration with investigators from the Keck School of Medicine of the University of Southern California.
The study leveraged a statewide resource of nearly 1,700 archived neonatal dried blood spots collected through routine newborn screening programs in California. Methylome profiles from newborns who later developed ALL were compared with age, sex, and demographically matched controls with no known leukemia diagnosis.
DNA methylation was selected as the primary epigenetic marker for analysis given its central role in transcriptional regulation, lineage commitment, and hematopoietic development. Differential methylation analysis across the genome was used to identify loci and regions associated with future leukemia risk.
Comparative analyses identified statistically significant methylation differences present at birth in neonates who later developed ALL. Among the strongest site-specific associations were loci within ARID5B, a gene previously implicated in ALL susceptibility through genome-wide association studies, providing convergent evidence linking genetic and epigenetic risk mechanisms.
Beyond individual loci, investigators reported more than 100 differentially methylated genomic regions (DMRs) distinguishing future ALL cases from controls. Many of these regions mapped to genes involved in early hematopoiesis or transcriptional regulation, including FLI1 and LAX1, which have established relevance to leukocyte differentiation and leukemia biology.
Collectively, these findings support the hypothesis that epigenetic alterations associated with ALL risk are detectable at birth, preceding both clinical diagnosis and the emergence of overt leukemic clones.
Prior epidemiologic and molecular studies have suggested that pediatric ALL may originate from in utero genetic lesions, such as chromosomal translocations detectable in neonatal blood spots. This study extends that framework by demonstrating that epigenetic variation is also present at birth, offering a complementary layer of early biological predisposition.
The authors propose that these neonatal methylation patterns may influence downstream gene expression programs involved in immune development, clonal expansion, or susceptibility to secondary postnatal insults that drive leukemogenesis.
Importantly, because DNA methylation can be modulated by maternal metabolism, nutritional status, and environmental exposures, the investigators note that these findings may eventually inform research into modifiable prenatal risk factors, although no causal relationships or intervention strategies have yet been established.