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Last Updated: Dec 18, 2012 - 10:19:55 AM
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The gene processes that drive acute myeloid leukaemia

Mar 27, 2011 - 4:00:00 AM
However, the team found that, despite mutations in this most frequently mutated leukaemia gene, only three out of every ten mice developed leukaemia and the disease developed only after a long time. The results suggest that the Npm1 mutation can start the leukaemic process but cannot, on its own, drive cells towards cancer.

 
[RxPG] Researchers have described how the most common gene mutation found in acute myeloid leukaemia starts the process of cancer development and how it can cooperate with a well-defined group of other mutations to cause full-blown leukaemia.

The researchers suggest that three critical steps are required to transform normal blood cells into leukaemic ones, each subverting a different cellular process. By charting the route towards cancer, the study identifies processes that might serve as targets for new treatments to halt the cancer's development in its tracks and even reverse it.

Acute myeloid leukaemia is a rare but devastating disease, which can take hold in a matter of just days or weeks. Every year, 2,000 adults in the UK are diagnosed with acute myeloid leukaemia: only about three in ten adults survive for five years.

In recent years researchers have identified a number of genes involved in the development of acute myeloid leukaemia. The most common is NPM1, a gene with many known functions. The new research shows that mutation in NPM1 is a key event in the development of a large proportion of cases of acute myeloid leukaemia and that it exerts its effect by helping cells to self-renew, a process that can be thought of as the first step towards leukaemia. The team also identify two subsequent events that are required to cooperate with NPM1 to drive cells to become cancerous.

We have used targeted gene disruption to look at the way acute myeloid leukaemia develops in mice, says Dr George Vassiliou, Consultant Haematologist, cancer researcher and first author on the study from the Wellcome Trust Sanger Institute, and have found critical steps that take place when the cancer develops. Identifying the biological steps in turn means we can look for new drugs to reverse the process.

The team started by developing a strain of mice that contained a 'control switch', that allowed the researchers to turn on mutations in the acute myeloid leukaemia gene Npm1.

When they switched on the Npm1mutations in the mice, the team saw that the mutation gave normal blood cells the ability to renew themselves more efficiently and boosted the production of a group of blood cells known as myeloid cells.

However, the team found that, despite mutations in this most frequently mutated leukaemia gene, only three out of every ten mice developed leukaemia and the disease developed only after a long time. The results suggest that the Npm1 mutation can start the leukaemic process but cannot, on its own, drive cells towards cancer.






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