Monday, July 14, 2008

Precise location of an oncogene may determine the onset of childhood leukemia

The white blood cells in our body combat foreign intruders, such as viruses and bacteria. In leukemia, the formation of white blood cells goes haywire and the cells that should develop into white blood cells multiply out of control without fully maturing. This process disrupts the production of normal blood cells, making patients more susceptible to infections. T-ALL, a particular form of leukemia, is the most prevalent cancer in children under 14 years of age and occurs predominantly between the ages of two and three.

With intensive treatment involving chemotherapy, over half of children are cured. But scientists hope to be able to develop targeted therapies that are less toxic than chemotherapy, based on knowledge of the biological processes behind T-ALL.

Oncogenes are often at the root of cancer. Scientists around the world are theefore concentrating on identifying oncogenes and their related proteins. Recent research by the Flanders institute of Technology in Belgium (VIB-K.U.Leuven) indicates that the location in the cell where these proteins are found plays an important role in the entire carcinogenic mechanism.

In collaboration with the Nederlands Kanker Instituut, Amsterdam and Harvard Medical School, Boston, the VIB researchers have demonstrated that NUP214-ABL1, a fusion of two proteins, is carcinogenic only when it is in a protein complex near the nucleus of the cell. Located at another place in the cell, NUP214-ABL1 does not lead to cancer. This finding sheds new light on the study of carcinogenic processes.

Many forms of cancer are caused by genetic defects in which a certain kinase becomes too active and this is the case with NUP214-ABL1. The most obvious solution is to make the carcinogenic kinase inactive, and so kinase inhibitors are usually used to combat these kinds of cancers. However, the carcinogenic kinase often becomes resistant to these inhibitors, which is certainly true for T-ALL. new approaches are therefore being actively sought.

The recent research results now offer a possibility. It has been shown in cells that NUP214-ABL1 is no longer carcinogenic when it cannot bind with the protein complex in the vicinity of the cell nucleus. On the basis of these results, the researchers want to further investigate the therapeutic possibilities of compounds that render binding between the complex and NUP214-ABL1 impossible. This study also indicates that the location of proteins can play an important role in other forms of cancer/leukemia as well.

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