Drug Prevents Disease In Mouse Model Of Leukemia

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Clinical Trials / Drug Trials;  Biology / Biochemistry
Article Date: 27 Aug 2007 - 11:00 PDT

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In a new study, Danilo Perrotti and colleagues from Ohio State University, Columbus, show that treatment with a drug known as FTY720 prevents disease in a mouse model of many leukemias caused by the cancer protein BCR-ABL (nearly all cases of blast crisis chronic myeloid leukemia [CML-BC] and some cases of acute lymphocytic leukemia [ALL]). As the drug also induced cell lines from humans with these leukemias to die in vitro the authors suggest that FTY720 should be considered by researchers and clinicians developing new approaches to treat CML-BC and ALL patients.

FTY720 was chosen for these studies because it does not directly target the BCR-ABL kinase, which in individuals with CML-BC and ALL is resistant to kinase inhibitors such as imatinib (Gleevec). Instead, FTY720 activates protein phosphatase 2A (PP2A), which is a tumor suppressor that is inactivated by signals induced by BCR-ABL. The pharmacologic doses of FTYY720 used to suppress leukemogenesis in the mice had no adverse effects and FTY720 has thus far shown no adverse effects in clinical trials testing its potential as a therapeutic for the treatment of multiple sclerosis. The authors therefore believe their data provide strong support for the use of FTY720 as a novel therapeutic for CML-BC and ALL patients that are not responsive to treatment with kinase inhibitors.

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TITLE: FTY720, a new and alternative strategy for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemia

AUTHOR CONTACT:
Danilo Perrotti
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.

Source: Karen Honey
Journal of Clinical Investigation

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