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Finding suggests a common childhood leukemia may form in the womb

Researchers led by a scientist who joined the UC San Francisco faculty last week are reporting that a genetic mutation implicated in a common form of childhood leukemia appears to occur in the womb.

Their study, reported in the Oct. 30 issue of Lancet, indicates that two genes, known as TEL and AML1, aberrantly fuse during the development of the blood cells in the fetus. The fused genes then produce a protein that is potentially oncogenic.

Based on previous research, the team says the fused state of the two genes is not inherited; instead, it occurs during pregnancy, probably as a result of a developmental accident, as opposed to exposure to an environmental mutagen.

Importantly, the fusion of the TEL and AML1 genes is not sufficient to cause development of the disease, known as "common acute lymphoblastic leukemia," the researchers said. All people have two copies of every gene, and earlier work by the researchers on identical twins with leukemia indicates that a second genetic alteration - involving the second copy of the TEL gene, one of the two so-called "alleles" -- occurs post-natally to actually nudge blood cells into a leukemic state.

"It may be that the normal TEL allele successfully suppresses the function of the aberrant TEL-AML1 protein resulting from the fusion, so full-blown leukemia doesn't occur," said the lead author of the study, Joseph Wiemels, PhD, now a UCSF assistant research molecular epidemiologist. "One theory is that the second, normal TEL allele is lost, and that at this point the fused TEL-AML1 protein becomes oncogenic."

The researchers don't know what leads to the initial genetic abnormality in the womb, but their discovery, said Wiemels, will provide researchers with a time frame for analyzing the development of the mutation. Studies indicate that the second genetic alteration may result from an abnormal reaction to common childhood infections.

Wiemels conducted the research in the laboratory of Mel Greave
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
1-Nov-1999


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