The overproduction of the BCL-2 protein is due to a defect in the ribosome, the protein factory of the cell. This defect is found in 10% of the pediatric patients with T-cell leukaemia.
Ribosome defects and cancer
"In the past couple of years, it has become clear that ribosome defects play a role in different types of cancer," explains Professor Kim De Keersmaecker, head of the Laboratory for Disease Mechanisms in Cancer at KU Leuven. "In the case of a ribosome defect, the cells still produce proteins but the balance between their quantities is slightly off, which leads to cancer."
Professor De Keersmaecker and Dr. Kim R. Kampen, a postdoc in her lab, were able to delineate the cancer promoting function of a specific ribosome defect that has a severe impact on pediatric patients with T-cell leukaemia. The impact of this ribosome defect on T-cell leukaemia has never been elucidated before.
Survival proteins
If a cell is too damaged due to ageing or disease, a specific signal induces cell death. But some proteins – including the protein known as BCL-2 – can put a stop to cell death. Due to a ribosomal defect, some T-cell leukaemia patients produce too much of this cell death preventing protein.
The overproduction of BCL-2 has detrimental effects, says Professor De Keersmaecker. "Cancer cells take advantage of the BCL-2 protein: it helps them to survive under difficult circumstances, including chemotherapy."
Suppressing the survival protein
A drug that suppresses BCL-2 is already used to treat another type of leukaemia.
"Clinicians use this drug to treat chronic lymphocytic leukaemia. But our research in mice shows that it also suppresses T-cell leukaemia with a specific ribosome defect."
Follow-up study
But it's too soon to talk about cure, De Keersmaecker warns. "This hasn't been tested on human beings yet."
"Patients with leukaemia often get a drug cocktail, while our study only tested the BCL-2 inhibitor. That's why our follow-up study will focus on a cocktail of this BCL-2 inhibitor and other drugs. For patients with the ribosome defect analyzed in our study, this avenue is definitely worth examining in greater detail."
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Funding
This study was funded by the European Research Council, Research Foundation – Flanders (FWO), Stichting Tegen Kanker, Kom op tegen Kanker and the Me2You Foundation.
About KU Leuven
KU Leuven is Europe's most innovative university. Located in Belgium, it is dedicated to research, education, and service to society. KU Leuven is a founding member of the League of European Research Universities (LERU) and has a strong European and international orientation. Our scientists conduct basic and applied research in a comprehensive range of disciplines. University Hospitals Leuven, our network of research hospitals, provides high-quality healthcare and develops new therapeutic and diagnostic insights with an emphasis on translational research. The university welcomes more than 50,000 students from over 140 countries. The KU Leuven Doctoral Schools train approximately 4,500 PhD students. http://www.kuleuven.be/english
Media Contact
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https://nieuws.kuleuven.be/en/content/2018/t-cell-leukaemia-cancer-cells-take-advantage-of-survival-protein
Related Journal Article
http://dx.doi.org/10.1038/s41375-018-0176-z
