Researchers Create A New Form Of Therapy For Leukemia And Lymphoma

ST. PAUL, Minn., Jul 1, 1999 /PRNewswire via COMTEX/ -- Researchers experimenting with cells and mice have created a new anti-leukemic drug which attacks and kills leukemia cells without side effects. The technique may be tested on humans this fall.

Dr. F. M. Uckun of the Hughes Institute, St. Paul, MN, said Tuesday WHI-P131 is actually a rationally designed small molecule that will inhibit a life-maintaining enzyme, known as JAK3, in leukemic cells.

"Normal tissue is not affected," he said, "Only the leukemia cells are going to die."

Uckun, senior author of a study that appeared in the journal Clinical Cancer Research said the same technique can also be used for treatment of allergic disorders since JAK3 plays a key role in allergy as well.

In the study, Uckun and his team treated human leukemia cancer cells. The cancer, called B-cell precursor leukemia, is the most common form of childhood cancer and the second most common form of acute leukemia in adults.

Uckun said earlier studies have shown that a molecule called JAK3 tyrosine kinase is essential for the survival of leukemia cells. The problem was how to completely block the action of JAK3 inside the cancer cells. And the solution was the novel compound WHI-P131. The development of WHI-P131 was aided by a 3D computer model of the protein JAK3 which demonstrated how the drug would interact with JAK3.

Uckun said the findings suggest a treatment that included cycles of first the drugs, then this JAK3 inhibitor could be very effective against leukemia.

Dr. Uckun's group now plans to seek Food and Drug Administration approval to test the drug on human leukemia patients. Uckun said clinical trials of the therapy should start this fall.

Clinical Cancer Research, which published the study, is the journal ofthe American Association of Cancer Research.

Reference: Sudbeck EA, Liu XP, Narla RK, Mahajan S, Ghosh S, Mao C, Uckun FM. Structure-based design of specific inhibitors of Janus Kinase 3as apoptosis-inducing antileukemic agents. Clinical Cancer Research, 5:1569-1582, 1999.