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St. Jude Researchers Identify Key Genetic Trigger of Acute Myeloid Leukemia
Date:11/27/2007

N-Myc gene lives a double life, triggering cancer when it works with the growth-promoting protein IL-3 and causing cell suicide in the absence of IL-3

MEMPHIS, Tenn., Nov. 27 /PRNewswire-USNewswire/ -- A gene called N-Myc leads a double life in certain white blood cells when it is overexpressed, helping to trigger acute myeloid leukemia (AML) under some conditions while triggering apoptosis, or cell suicide, under other conditions, according to results of a mouse study done by investigators at St. Jude Children's Research Hospital.

"Since N-Myc overexpression frequently occurs in human AML as well, this discovery gives researchers an important insight into N-Myc's role in human AML," said Gerard Grosveld, Ph.D., chair of the St. Jude Department of Genetics and Tumor Cell Biology. "It also might contribute to new strategies for treating this leukemia or disrupting this gene's ability to cause it." Grosveld is senior author of a report on this work that appears in the Nov. 15 issue of "Cancer Research."

The researchers showed that artificially forcing overexpression of N-Myc in bone marrow cells of mice strongly promotes AML; and that levels of N-Myc RNA (the decoded form of a gene) from 137 patients with AML were between two- and 33-fold higher than in normal bone marrow cells.

The team also showed that myeloid cells that were genetically engineered to overexpress N-Myc became immortalized, or had an unlimited life span, and that this was associated with changes in levels of certain proteins known to occur when human myeloid cells become leukemic.

The St. Jude team demonstrated in cell cultures that N-Myc can also trigger apoptosis and kill the cell instead of making it reproduce uncontrollably. Specifically, most myeloid cells over-expressing N-Myc died within 24 hours when they were deprived of an anti-apotosis, growth-promoting protein called IL-3. In addition, there was a significant decrease in the activity of
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SOURCE St. Jude Children's Research Hospital
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