Immunosuppressant Drug Prevents Leukemia in Mouse Model

Cancer researchers have found that a drug currently being tested as a treatment for multiple sclerosis is effective in treating leukemia in a mouse model.

FTY720 (fingolimod) is a novel immunosuppressant drug that causes lymphopenia by redirecting lymphocytes from circulation to the lymph nodes. It is a structural analogue of sphingosine and a chemical modification of the ISP-1 metabolite of the fungus Isaria sinclairii.

Investigators at Ohio State University (Columbus, USA) evaluated the effectiveness of FTY720 as a chemotherapeutic agent for the treatment of leukemias initiated by the cancer protein ABL/ BCR. The ABL gene is located on the 9th chromosome, but it is activated by translocation to the BCR (breakpoint cluster region) gene on chromosome 22. The new ABL/BCR (chimeric) gene encodes a tyrosine kinase, which allows the cells to proliferate without being regulated by cytokines. This in turn allows the cell to become cancerous.

Results of the study carried out on a mouse model of human leukemia were published in the August 23, 2007, online edition of the Journal of Clinical Investigation. These results showed that FTY720 prevented development of ABL/BCR leukemia in the mouse model. In addition, the drug induced human ABL/BCR leukemia cell lines to undergo apoptosis in vitro. FTY720 functioned by activating protein phosphatase 2A (PP2A), a tumor suppressor that is inactivated by signals induced by ABL/BCR. No toxic effects were detected from the pharmacologic doses of FTY720 used to suppress development of leukemia in the mice.

The researchers concluded that their data provided strong support for the use of FTY720 as a novel therapeutic for leukemia patients that were not responsive to treatment with kinase inhibitors.


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