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Key player found for a cancer typical in Down syndrome
Date:3/1/2010

Boston, Mass. Between 5 and 10 percent of babies with Down syndrome develop a transient form of leukemia that usually resolves on its own. However, for reasons that haven't been clear, 20 to 30 percent of these babies progress to a more serious leukemia known as Down syndrome acute megakaryoblastic leukemia (DS-AMKL), which affects the blood progenitor cells that form red blood cells and platelets. Now, researchers at Children's Hospital Boston have found a gene regulator they believe to be a key player in DS-AMKL, advancing understanding of how the disease develops and how to treat it.

The study findings, published in the March 1 issue of Genes and Development, may also help in understanding other forms of leukemia, the researchers say.

The gene regulator, miR-125b-2, belongs to a class of molecules known as microRNAs, which silence gene expression by halting the manufacturing of different proteins. While microRNAs are important to normal cell function, unusual amounts of them can lead to disease. "DS-AMKL has a very strong genetic basis," says senior investigator Stuart Orkin, MD, of the Division of Hematology/Oncology at Children's. "However, there aren't that many cancers in which a particular microRNA can be pointed to as contributing."

Because children with Down syndrome have three copies of chromosome 21 rather than the usual two copies, the researchers focused on the five microRNAs produced by this chromosome, and zeroed in on miR-125b-2.

"In human primary DS-AMKL cells, this microRNA is quite dramatically over-expressed," says Zhe Li, PhD, of Children's Division of Hematology/Oncology and first author of the paper. "We then went back and studied how over-expression or downregulation of this microRNA affects the phenotype of leukemia cells."

DS-AMKL is always associated with mutations in the gene GATA1, which helps make and regulate red blood cells and megakaryocytes (the cells that produce platelets
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Contact: Rob Graham
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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