(Memphis, Tenn. June 10, 2013) Changes in an epigenetic mechanism that turns expression of genes on and off may be as important as genetic alterations in causing pediatric acute lymphoblastic leukemia (ALL), according to a study led by scientists at St. Jude Children's Research Hospital and published in the June 10 online edition of the Journal of Clinical Investigation.
The results suggest the mechanism called cytosine methylation plays a previously under-appreciated role in the development of leukemia. Cytosine methylation involves adding or removing methyl groups to cytosine, which is a building block of DNA.
The study is the most comprehensive effort yet to identify and understand genetic and epigenetic factors that work together to cause ALL, the most common childhood cancer. ALL is a cancer of white blood cells known as lymphocytes. Scientists at St. Jude and Weill Cornell Medical College collaborated on the project.
Researchers used a variety of techniques to examine hundreds of thousands of methylation sites across the genome in normal and leukemic lymphocytes, including samples from more than 160 children with ALL. Investigators found that known ALL subgroups, which are defined by chromosomal alterations, have unique methylation profiles. Those profiles correlated with different patterns of gene expression.
"It is well known that different leukemia subgroups have distinct patterns of gene expression that are important in the development of leukemia," said Charles Mullighan, MBBS (Hons), MSc, M.D., an associate member of the St. Jude Department of Pathology. Mullighan and Ari Melnick, M.D., Gebroe Professor Hematology/Oncology at Weill Cornell Medical College, are the study's co-corresponding authors.
"We have assumed that the underlying genetic changes are important determinants of those gene expression profiles. We now know that changes in methylation state also have key roles in influencing gen
|Contact: Carrie Strehlau|
St. Jude Children's Research Hospital