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Gene-inactivating agent in leukaemia treatment

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The Pharmaceutical Journal Vol 265 No 7109p223
August 12, 2000 Clinical

Gene-inactivating agent in leukaemia treatment

A ribozyme designed to kill chronic myelogenous leukaemia (CML) cells completely inhibits tumour-cell infiltration in a CML mouse model, say Japanese researchers.
CML is associated with the expression of a chimeric BCR-ABL gene (oncogene) that yields an oncoprotein on translation. This protein has tyrosine kinase activity which causes malignant transformation of white blood cells in CML.
The researchers had designed the ribozyme that, in earlier cell culture experiments, specifically cleaved BCR-ABL mRNA, inducing apoptosis in CML cells. The ribozyme remains inactive in the presence of normal mRNA, say the researchers. In the new study, a mouse model for CML was used to test the ribozyme's inactivation of the oncogene. Two groups of mice were injected with CML cells with or without the ribozyme. Survival of the animals was monitored daily for 100 days after inoculation. All the animals injected with control CML cells died, with a median survival time of nine weeks. At 100 days after inoculation, all mice injected with CML cells with ribozyme remained healthy.
The researchers say that their results raise the possibility that the ribozyme could be useful for treating human sufferers, by "purging" bone marrow in cases of CML treated by autologous transplantation. The study is published in Nature (2000;406:473).

Citation: The Pharmaceutical Journal URI: 20002488

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