Application of Epigenetic Markers for Early Detection of Childhood Leukemia.

Childhood leukemia is the most common cancer in children, and a devastating illness to a child and family. Treatments have improved; however, still too many children die, and those that live face a lifetime of reduced health and uncertainty.  Our work is focused on epidemiology and prevention of this disease.  We ask questions: what are the  aberrations that cause leukemia?  How does our environment interact with our bodies to produce these aberrations?  When do mutations occur, and in knowing this can we develop early detection tests and prevention strategies such as vaccines?  To approach prevention we need to know the deepest intricacies of the etiology of disease.  Our focus for the current project is to build a better understanding of the "epigenetics" of leukemia, and find out whether epigenetic markers can be used to help detect leukemia early.  Epigenetics is the study of the way that genes are controlled.  The most basic epigenetic mark is a "methyl" chemical group that can be added to gene control regions; this "methyl" tends to turn genes off.  When genes that are critical in the control of cell growth control are turned off in this fashion, this can contribute to cancer. In childhood leukemia, very few studies have looked at gene methylation, and because of this we propose to look comprehensively so that we can discover the full complement of methylation changes in leukemia samples from our Northern California Childhood Leukemia Study.  We will be able to characterize the critical methylation changes (out of a library of 27,000), which we will then test as "early detection markers" for leukemia by testing for their presence in neonatal heel-prick blood cards (Guthrie cards).  We will also test whether these genes are "turned off" in any percentage of newborns that did not contract leukemia (study controls), which will determine their specificity for leukemia.  Our study therefore aims at improving our understanding of the epigenetics of childhood leukemias, and discovering new markers that can be used to gauge the risk of developing leukemia.