The findings, as published in the journal Molecular Cancer, show that these markers have proven to be crucial indicators for predicting patient survival. This promising research could pave the way for earlier diagnosis and more effective therapeutic interventions for childhood leukemia, which remains the leading cause of cancer-related deaths in children.
Prof. Terry Dwyer states "This research reveals epigenetic markers at birth that predict risk of pediatric leukemia and that are found in cancer causing cells at the onset of disease. These findings offer new hope for early diagnosis and potential therapeutic interventions in childhood cancer, which is the leading cause of death in children"
Epigenetic Markers Found in Blood Could Predict Childhood Leukemia Risk and Survival
The study used a novel approach to trace the molecular origins of leukemia from birth. By profiling molecular "maps" in patients at various stages of their illness—birth, diagnosis, remission, and recurrence—the researchers focused on the epigenome. This molecular system governs how genes are expressed and interacts with both genetic inheritance and environmental factors, such as those a child might be exposed to during pregnancy.
It's core discovery lies in how these epigenetic imprints, captured through blood samples, provide a snapshot of early-life exposures that could influence the development of leukemia later in life. This offers an unprecedented opportunity to identify at-risk children before the disease manifests, ultimately enabling much earlier intervention and potentially improving survival rates.
"This research opens new avenues for understanding the early molecular origins of childhood leukemia. It shows how environmental and genetic factors can interact to create a molecular blueprint that may influence the development of cancer years later," said Dr. Zdenko Herceg, co-author of the study.
Groundbreaking Study Tracks Cancer Origins From Birth, Offering New Hope for Early Diagnosis
In a breakthrough that addresses longstanding gaps in pediatric cancer research, the study overcame a major challenge: the reliance on clinical samples collected after disease onset. Previous research often faced the issue of "reverse causality," where biological changes could result from the cancer itself rather than being the cause of it.
To solve this, the team turned to archived Guthrie cards—small blood samples routinely collected from newborns as part of neonatal screening programs. These blood spots, often collected from heel pricks at birth, served as the starting point for analyzing epigenetic markers. This novel approach revealed potential early epigenetic changes that could act as precursors to leukemia, detectable at birth, long before the disease appears clinically.
The researchers followed patients over a decade, confirming that DNA methylation alterations present at birth could serve as significant biomarkers for ALL development, prognosis, and survival. These findings suggest that early-life epigenetic changes may be reversible, especially in patients who respond well to therapy, offering new possibilities for personalised treatments.
“Because childhood cancer may have origins in utero, we have essentially travelled back in time to collect blood samples at birth from children who later developed cancer,” says IARC scientist Dr Akram Ghantous, the lead author of the study. “We are mapping the molecular ‘diaries’ of nature and nurture in patients with cancer while tracing these diaries back to birth – in a way, reversing the arrow of time to uncover early origins of the disease.”
Research Identifies Reversible Epigenetic Changes as Key Biomarkers for Personalised Leukemia Treatment
The study's findings, which were reproducible across different technologies, populations, and continents, provide strong evidence that DNA methylation changes are key indicators of leukemia risk. These methylation patterns—changes to the DNA that do not alter the genetic code but affect gene activity—are particularly important because they are reversible. This suggests that therapeutic interventions could alter these changes and potentially improve patient outcomes.
In addition to being validated in diverse ethnic groups—including the often-underrepresented Hispanic population, who have the highest rates of childhood leukemia worldwide—these findings have the potential to change how we approach the early detection and treatment of paediatric ALL.
As Dr. Zdenko Herceg explains, "This study is the result of a large-scale multidisciplinary effort, substantial investment, and extensive international collaboration. By combining epidemiology, clinical oncology, and advanced laboratory science, we have gained unique insights into the causes of cancer and identified biomarkers that could lead to early detection and personalised risk stratification and therapy."
What’s Next: Effective Pediatric Cancer Treatments
Looking ahead, the research team plans to expand their study to include larger and more diverse populations. This will help uncover additional molecular precursors of childhood leukemia and refine clinical applications. The hope is that, with further validation, the biomarkers identified in this study could lead to a new era of early cancer detection—ultimately saving lives by enabling personalised treatment plans that target cancer before it fully develops.
With this study, the scientific community moves closer to understanding the early molecular origins of childhood leukemia, offering new hope for better detection, prevention, and treatment of this devastating disease.