Not the protein, but its location in the cell, determines the onset of leukemia

July 10, 2008

Scientists are still searching for the cause of many forms of Leukemia, including T-cell acute lymphoblastic leukemia. VIB researchers connected to the Katholieke Universiteit Leuven have discovered that the carcinogenic property of the fusion protein NUP214-ABL1 largely depends on its location in the cell. Casting new light on the biological processes behind T-ALL, this finding is important in the search for new targeted therapies that are less toxic than chemotherapy.

The white blood cells in our body combat foreign intruders, such as viruses and bacteria. However, in leukemia, the formation of white blood cells is disturbed: 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. At the moment, with an optimal treatment using chemotherapy, over half of the 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. So, scientists around the world are concentrating on identifying oncogenes and their related proteins. Recent research by Kim De Keersmaecker and colleagues in Jan Cools' research group (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 Maarten Fornerod (Nederlands Kanker Instituut, Amsterdam) and Gary Gilliland (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. So, scientists are actively seeking alternative approaches.

De Keersmaecker's recent research results now offer a possibility. Indeed, the scientists have 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.

Source: VIB (the Flanders Institute for Biotechnology)

Explore further: Trio wins Nobel Prize for mapping how cells fix DNA damage

Related Stories

Trio wins Nobel Prize for mapping how cells fix DNA damage

October 7, 2015

Tomas Lindahl was eating his breakfast in England on Wednesday when the call came—ostensibly, from the Royal Swedish Academy of Sciences. It occurred to him that this might be a hoax, but then the caller started speaking ...

Parasite growth hormone pushes human cells to liver cancer

October 9, 2009

Scientists have found that the human liver fluke (Opisthorchis viverrini) contributes to the development of bile duct (liver) cancer by secreting granulin, a growth hormone that is known to cause uncontrolled growth of cells. ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.