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 paediatric patients with T-cell leukaemia.

"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 paediatric patients with T-cell leukaemia.

The impact of this ribosome defect on T-cell leukaemia has never been elucidated before.

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."

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."

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."

Source: KU Leuven