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

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)

Related stories:

Faulty DNA repair could be a risk factor for lung cancer in nonsmokers
People who have never smoked but whose cells cannot efficiently repair environmental insults to DNA are at higher risk of developing lung cancer than those with effective genomic repair capability, according to researchers from the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center.
Cellular message movement captured on video
Proper signaling step required for controlled cell growth -- otherwise, cancer and other diseases can result
Scientists have captured on video the intracellular version of a postal delivery service. Reporting in the journal Biochemical and Biophysical Research Communications (BBRC), bioengineering researchers at UC San Diego published videos of a key message-carrying protein called paxillin moving abruptly from hubs of communication and transportation activity on the cell surface toward the nucleus. Paxillin was labeled with a red fluorescence marker to make it stand out in live cells.
Drug used to prevent HIV transmission from mother to child damages DNA
HIV transmission from mother to child can occur in utero, during labor or from breastfeeding. If left untreated, approximately 25 percent of newborns exposed to the virus from their infected mothers will become infected themselves and potentially develop AIDS. Fortunately, antiretroviral drug combinations, which typically include AZT (zidovudine), a nucleoside reverse transcriptase inhibitor (NRTI), have reduced the rate of transmission from mother to child to less than 2 percent in infants who are not breast fed.
Suspicion lingers over bisphenol A and breast cancer
Bisphenol A, a common industrial chemical claimed to speed the growth of human breast and ovarian cancers, retains its carcinogenic properties even after being modified by body processes, report Indiana University and University of California at Berkeley scientists in the Aug. 28th issue of Chemistry & Biology, a Cell Press journal.
Quantum Dots Pose Minimal Impact to Cells
Nano-sized fluorescent probes that can slip inside living cells and elucidate life’s most fundamental processes, or track the effectiveness of cancer-fighting drugs, are barely noticed by the cells they enter, according to a team of researchers led by the U.S. Department of Energy’s Lawrence Berkeley National Laboratory.
Scientists May Have Solved Mystery Of Carcinogenic Mothballs
Chemical compounds in household products like mothballs and air fresheners can cause cancer by blocking the normal process of "cell suicide" in living organisms, according to a new study spearheaded by the University of Colorado at Boulder.
Cancer is colour-blind
We may look different on the outside, but inside we are all the same - so much has been scientifically proven. Research at the University of Bergen has shown that the pathways that lead to cancer are similar, no matter where you come from.
Scientists use bacteria to pinpoint chloride toxins
Scientists have studied the sensor with which bacteria detect chloride compounds, many of which can be carcinogenic or dangerous to the environment, and now hope to speed up identification of these dangerous toxins from weeks to just a few hours.
Dr David Leys at the University of Manchester’s Faculty of Life Sciences has won a prestigious European Research Council (ERC) starting grant to further understand this process and to develop a biosensor that will alert us to contamination in environmental or foodstuff samples quickly.

News discussion:

Medicine & Health news