Prenatal Exposures, DNA Methylation & Childhood Leukemia

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Investigator: Joseph Wiemels, PhD
Sponsor: University of California Berkeley

Location(s): United States

Description

At the cellular level pediatric leukemias like other cancers are caused by genetic and epigenetic alterations. Distinct subtypes of cytogenetic abnormalities have been recognized in childhood ALL for many years and are cornerstones of leukemia patient management and more recently, epidemiology studies. Recent studies on the epigenetics of leukemia suggest that alterations including DNA methylation are common and potentially important features of childhood ALL. Our preliminary studies and those of others have shown that DNA methylation events in leukemia are complex. Some events are reflective of the normal developmental epigenetic programs and therefore the events simply mirror the normal biology of the progenitor population of cells that were transformed. Other events are acquired during the transformation process. Some may arise from early epigenetic aberrations resulting from environmental exposures and developmental abnormalities. In this project we will attempt to delineate the critical DNA methylation events in pediatric leukemias and furthermore define those influenced by the environment, particularly in the prenatal period. The development of a panel of exposure- and leukemia-related biomarkers is the goal, which could be utilized in future biomonitoring, risk stratification, and epidemiology studies. We will characterize the DNA methylation pattern of normal B-cell progenitors and a series of leukemia bone marrow samples (n=250) using a high dimension technology, to define the DNA methylation events critical in leukemia. Second, we will utilize the same technology to define the DNA methylation pattern at birth on same 250 leukemia cases and their case bloods using neonatal dried blood spot (DBS) DNA.