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Researchers make critical leukemia stem cell discovery
Date:12/13/2010

eukaemia, in part by activation of beta-catenin. But suppression of beta-catenin in leukaemic stem cells reduced leukaemic cell growth, delayed the onset of leukaemia and reversed the stem cells to a pre-leukaemic stage. Furthermore, when beta-catenin was completely inactivated in mice with pre-leukaemic cells, the mice did not develop leukaemia, even though they carried MLL gene mutations.

Researchers then wanted to see how suppression of the beta-catenin protein impaired human leukaemic cells. They found that suppression of the protein in MLL leukaemic cells again diminished their ability to proliferate and renew themselves (an essential part of how leukaemia develops). This confirmed the important role of beta-catenin in the human disease.

The study also revealed a previously unrecognized critical function of beta-catenin in mediating drug resistant properties of leukaemic stem cells. Leukaemic stem cells can become resistant to treatment in some cases but, crucially, this study showed that suppression of beta-catenin in human MLL leukaemic cells made them sensitive again.

Professor Eric So, who led the study at King's, said: 'These results are extremely exciting and represent a critical step forward in the search for more effective treatments for this devastating form of leukaemia. The findings provide compelling evidence that this protein could be exploited to develop an effective therapeutic target for this form of the disease.

'Most of the current anti-cancer therapies used to treat leukaemia attack healthy blood cells as well as cancerous ones. Interestingly, beta-catenin is not required for normal blood stem cells. So if we can specifically target beta-catenin in the bone marrow, we can have potentially a more effective and less toxic anti-leukaemia therapy that can efficiently eradicate leukaemic stem cells but spares healthy blood stem cells.

'Much more research needs to be done before we can adopt this approach
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Contact: Emma Reynolds
emma.reynolds@kcl.ac.uk
44-207-848-4334
King's College London
Source:Eurekalert

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