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Updated: Mar 27, 2026
Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients
Published on: June 16, 2017
The impact of periconceptional folate on the DNA methylome of acute lymphoblastic leukemia
Eric M Nickels1,2, Libby M Morimoto3, Alice Y Kang3
1Cancer and Blood Disease Institute, Children's Hospital Los Angeles, Los Angeles, CA, USA. enickels@chla.usc.edu.
Insights
Periconceptional folate intake, especially from natural foods, may lower childhood acute lymphoblastic leukemia (ALL) risk by influencing early DNA methylation patterns. This study identified specific DNA methylation sites linked to folate exposure and ALL risk.
Area of Science:
- Epigenetics
- Nutritional Epidemiology
- Pediatric Oncology
Background:
- Periconceptional folate intake is linked to reduced risk of pediatric acute lymphoblastic leukemia (ALL).
- The underlying biological mechanisms connecting folate, DNA methylation, and ALL development remain unclear.
Purpose of the Study:
- To identify DNA methylation sites at birth that are influenced by periconceptional folate intake.
- To find methylation sites associated with lymphoblasts at ALL diagnosis using a "meet in the middle" approach.
Main Methods:
- Retrospective analysis of maternal dietary folate intake and neonatal dried blood spot DNA methylation data.
- Epigenome-wide association study comparing 189 ALL cases and 205 controls from the California Childhood Leukemia Study (1995-2008).
- Identification of folate-associated differentially methylated regions (DMRs) overlapping with lymphoblast-associated DMRs.
Main Results:
- Overlapping DMRs were found for total, food, natural, fortified, and supplemental folate intake.
- A majority of overlapping DMRs showed a concordant effect for supplemental folate.
- Opposite methylation effects were observed for food and natural folate in lower-income participants, particularly Hispanic individuals.
Conclusions:
- Dietary folate, especially from natural food sources, may mitigate ALL risk by modulating early-life DNA methylation patterns.
- The impact of folate on DNA methylation and ALL risk may differ based on folate source and socioeconomic factors.
- This research highlights potential epigenetic pathways linking nutrition and childhood leukemia.
Abstract:
Periconceptional folate intake decreases the risk of pediatric acute lymphoblastic leukemia (ALL); however, the mechanism is not fully understood. We sought to identify sites of DNA methylation measured at birth both responsive to periconceptional folate and associated with lymphoblasts at the time of ALL diagnosis in a "meet in the middle" analysis. Folate-associated differentially methylated regions (DMRs) were identified from retrospectively collected periconceptional maternal folate intake (by dietary source) and epigenome-wide DNA methylation status from archived dried neonatal blood spots for 189 ALL cases and 205 healthy matched controls from the California Childhood Leukemia Study (1995-2008). Folate and lymphoblast-associated DMRs overlapped at 17 sites related to total folate intake, 13 for folate from food, 10 for natural foods, 13 for fortified foods and 18 for folate-containing supplements. The majority of overlapping DMRs were in a concordant direction of effect for supplemental folate (16/18, P = 0.001). Opposite direction of effect was identified among lower income participants for food (3/19, P = 0.004) and natural folate (5/37, P < 0.001), the latter of which was specific to Hispanic participants of low-income (9/31, P = 0.029). These results indicate that dietary folate, in particular from natural food sources, may reduce risk of ALL through modulation of early DNA methylation patterns.
