WASHINGTON- The discovery of a novel genetic mechanism for some kinds of leukemias provides researchers with new hope for identifying difficult cases and a new avenue of research for developing novel treatments.

By observing chromosomal rearrangements, cancer researchers have been able to locate a number of leukemia genes. This has provided essential information for the development of diagnostic tests. The ALL1 gene is one of the most important of the leukemia genes. The ALL1 gene was first discovered in association with chromosomal rearrangements. Now researchers have identified the ALL1 gene in leukemias without chromosomal rearrangements. This suggests that the gene may be involved in twice as many cases of leukemias than was previously believed.

Gene fusion normally refers to the juxtaposition of segments from two different genes. Indeed, previous genetic defects observed in association with different leukemias have involved genes combining with parts of other genes. The new defect is unique in that it fuses to a partial copy of itself.

"We were interested to know whether there could be any rearrangements of the ALL1 gene in patients for whom no visible chromosomal rearrangements were present. I worked with this for several months. It was a puzzle basically that I was trying to solve. The gene was rearranged and I was trying to discover the structure of the rearrangement. When I finally solved the problem I realized that I had discovered something wonderful, something unexpected and something that was bound to help people in the future," Steven Schichman, M.D., Thomas Jefferson University, Philadelphia, PA.

The ALL1 gene defect is acquired during the cell growth cycle rather than inherited. As a result of the defect the cell avoids normal growth regulation and grows uncontrolled eventually developing into a leukemia.

The ALL1 defect was seen in patients with trisomy 11, a condition characterized by an extra copy of chromosome 11. This is the first identification of a specific gene defect associated with trisomy in leukemia.

The self-fusion defect has so far only been associated with a type of leukemia called acute myeloid leukemia This leukemia progresses quite rapidly and has a poor prognosis. The researchers are now trying to identify other types of leukemia in which the gene defect may be involved.

The discovery of this gene defect in ALL1 should lead to a means of identifying a subgroup of patients with the worst prognosis and the highest risk of relapse. This in turn could lead to new treatments for patients with a poor outcome with current therapies, notes Schichman.

"The identification of gene defects in leukemia is very important because the defects lay the foundation for all future studies regarding ho leukemia actually grows and behaves. They also lay the foundation for the development of future therapies for those leukemias. Whenever you identify a gene defect, you have a potential target fro therapy in the future. Prior to identifying the ALL1 self-fusion defect, we didn't know how these leukemias occurred on a genetic basis, and now we do," he added.

The complete details of this study can be found in JAMA, 2/15/95, Vol. 273, No.7, pp 571-576.

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