Leukaemia is caused when a mutation occurs which allows our blood cells to divide and proliferate uncontrollably, so that defective blood cells displace the healthy blood cells. It has been known for some time that around a tenth of all AML patients have a mutation in a protein called C/EBPalpha, but until now it was unclear whether this mutation was the cause of the disease.
In this latest study, the researchers created a mouse with this mutation. Their work revealed that the mutation is indeed the cause of the disease, as it triggers genetic programmes which cause the white blood cells to proliferate uncontrollably.
The study threw up some surprises; it was once thought that myeloid leukaemia was caused by the uncontrolled proliferation of malignant blood stem cells. Instead, it now appears that this mutation acts on cells which are already turning into mature blood cells. The mutation reprogrammes these cells, causing them to proliferate and produce numerous, defective daughter cells. As these cells displace the healthy blood cells, they compromise the ability of the blood to transport oxygen around the body.
"This is the first time that non-stem cell myeloid leukaemia has been generated within a healthy blood system," commented Claus Nerlov of the European Molecular Biology Laboratory's Mouse Biology Unit in Monterotondo, Italy. "The findings will have profound implications for our understanding of the development and treatment of leukaemias."
The scientists identified a genetic programme which was triggered by the mutation and found that it is similar to the programme triggered by other mutations linked to other leukaemias. Currently, efforts to develop anti-leukaemia drugs are focused on these mutations, but the new findings suggest that it could be better to focus on the genetic pathways which are shared by many different cancer stem cells.
EU support for the work came from the EuroCSC ('Targeting cancer stem cells for therapy') project, which is funded under the 'Life sciences, genomics and biotechnology for health' thematic area of the Sixth Framework Programme (FP6).
Copyright ©European Communities, 2008
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