A Review on the Relationship Between Maternal Environment and Pediatric ALL Initiation and Progression: The Role of Early-Life Epigenetic Modifications

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, yet its etiology remains incompletely understood, particularly regarding the interplay between genetic, epigenetic, and environmental factors. This review explores how early-life epigenetic modifications contribute to ALL initiation and progression, with a focus on maternal influences. Unlike genetic mutations, epigenetic changes are reversible and shaped by environmental exposures, making them critical in leukemia risk and prognosis.

Maternal folate levels and metabolic conditions can alter fetal DNA methylation, influencing hematopoietic development. Folate provides methyl groups necessary for maintaining genomic stability, and its deficiency during pregnancy can lead to DNA hypomethylation, disrupting gene regulation and potentially fostering leukemogenesis, the process by which normal hematopoietic cells transform into malignant leukemia cells. Similarly, maternal diabetes, through hyperglycemia and insulin-like growth factor 1 overproduction, induces oxidative stress and epigenetic changes that may predispose offspring to ALL.

Epigenetic alterations, such as DNA methylation changes, can have distinct signatures linked to prognosis and therapeutic response. These findings highlight their potential as early biomarkers and targets for intervention. However, the field lacks longitudinal studies tracking epigenetic changes from birth to diagnosis.

By integrating research on maternal environmental
factors and leukemia-associated epigenetic modifications, this review underscores the need for further investigation into potential pathways linking maternal exposures to epigenetic programming and subsequent leukemogenesis. Understanding these mechanisms could improve early detection, predict prognosis, and inform targeted therapies for pediatric ALL.