Researchers who have studied the activity of thousands of genes in a drug-resistant form of childhood leukemia are now proposing that the disease be called mixed-lineage leukemia (MLL) because it is a distinct disease, and not a subtype of the more prevalent acute lymphoblastic leukemia (ALL).
The research team, which was led by Howard Hughes Medical Institute investigator Stanley J. Korsmeyer and colleague Todd Golub, both at the Dana-Farber Cancer Institute at Harvard Medical School, published its findings in the December 3, 2001, issue of Nature Genetics.
According to Korsmeyer, researchers had known that infants with a form of ALL characterized by a specific chromosome break and rearrangement on chromosome 11, called a translocation, suffered severe relapses after chemotherapy. Researchers had discovered that the translocation involved a gene that they called the mixed lineage leukemia gene, or MLL.
Korsmeyer, Golub and their colleagues theorized that the MLL translocation might cause aberrations in metabolic pathways that would indicate that the drug-resistant form of leukemia they were studying was genetically different from ALL, and thus a distinct form of leukemia. They decided to use DNA microarrays to test their hypothesis by comparing the expression of genes in the lymphocytes of children with classic ALL versus lymphocytes from children with the chromosome 11 translocation.
DNA microarrays, popularly known as gene chips, are large collections of genes that are arrayed on a postage-stamp-sized chip. To study gene activity in cells, researchers extract collections of RNA from cells and apply those collections to the microarray. By measuring the level of fluorescence of markers attached to the RNA, the researchers are able to determine the level of gene activity, or expression, of each gene.
In their studies, the scientists compared
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
3-Dec-2001