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An unexpected way to cause leukemia
Date:4/7/2008

Leukaemia cancer of blood or bone marrow is caused by mutations that allow defective blood cells to accumulate and displace healthy blood. To devise effective therapies it is crucial to know which mutations cause leukaemia and which cell type gives rise to leukaemic cells. Researchers from the European Molecular Biology Laboratory (EMBL) in Italy, the EMBL-European Bioinformatics Institute, UK, and the Universities of Harvard, USA, and Lund, Sweden, have now used genetic engineering to introduce a mutation found in human leukaemia patients into mice. In the current issue of Cancer Cell they report that the mutation causes leukaemia by triggering innate genetic programmes that allow white blood cells to proliferate uncontrollably. The findings have implications for the way leukaemia should be treated.

Blood is generated from a small number of multipotent stem cells that divide, differentiate and give rise to the many different cell types that make up the blood. At the same time they also maintain the pool of stem cells through a process called self-renewal. While differentiating, cells acquire specific properties and functions, but lose the capacity to self-renew in the way stem cells do. Mutations interfering with this process and promoting uncontrolled proliferation of certain blood cells can lead to leukaemia. Researchers of the group of Claus Nerlov at EMBLs Mouse Biology Unit now prove that a mutation in a protein called C/EBPa causes acute myeloid leukaemia (AML), a type of leukaemia affecting one lineage of white blood cells, in mice.

10 percent of all patients suffering from AML have this mutation, but we could never be sure if it causes the disease. By precisely reproducing the human mutation in the mouse we now proved a causative relation, says Peggy Kirstetter, who carried out the research in Nerlovs lab.

Instead of promoting uncontrolled proliferation of malignant blood stem cells, as often assumed as the cause of leukae
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Contact: Anna-Lynn Wegener
wegener@embl.de
49-622-138-7452
European Molecular Biology Laboratory
Source:Eurekalert

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