Cancer researchers have shown that some patients with T-cell leukemia produce too much of the BCL-2 protein. Cancer cells take advantage of this ‘survival protein,’ which allows them to escape chemotherapy. A drug suppressing this BCL-2 shows promising results.

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 leukemia.

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

Survival proteins

If a cell is too damaged due to aging 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 leukemia 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 leukemia.

“Clinicians use this drug to treat chronic lymphocytic leukemia. But our research in mice shows that it also suppresses T-cell leukemia 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 leukemia 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.”

The study was published in the journal Leukemia.