Defective ‘protein factory’ behind aggressive form of leukemia
Scientists have identified a defect in the ribosome, the protein factory of the cell in 20 to 40 per cent of the patients with multiple myeloma – a type of leukemia. These patients have a poorer prognosis than patients with intact ribosomes, the researchers said. At the same time, they respond better to a drug that already exists, according to the new study by University of Leuven (KU Leuven) in Belgium. Multiple myeloma (MM), also known as Kahler’s disease, is a blood cancer whereby the plasma cells in the bone marrow start proliferating malignantly. MM cannot be cured and is most common among older people. Various treatments exist to temporarily suppress the disease, but the challenge is determining to which treatment the patient will respond best. “In MM patients, one part of the ribosome is produced less in 20 to 40 per cent of the patients, depending on how aggressive the cancer is,” said Isabel Hofman, doctoral student at KU Leuven, “We suspect that their cells are still producing protein, but that the balance is somewhat disrupted. In any case, we found that these people have a poorer prognosis than MM patients with an intact ribosome,” said Kim De Keersmaecker, head of the KU Leuven Laboratory for Disease Mechanisms in Cancer. One possible treatment for MM is the use of proteasome inhibitors. “The proteasome is the protein demolition machine in a cell. There’s a type of drugs, including Bortezomib, that inhibits its functioning,” said De Keersmaecker. “How the defects in the ribosome influence the proteasome is not quite clear yet. But we discovered that patients with a defective ribosome respond better to Bortezomib,” she said. “In other words, their poorer prognosis can be offset by this treatment,” she said. “On the basis of these findings, we can now develop tests to identify defects in the ribosome and thus determine which therapy will have most effect in a specific patient,” said De Keersmaecker. The notion that cancer is related to ribosome defects is a relatively new concept in science. “A few years ago, we discovered defects in the ribosome of patients with acute lymphatic leukemia. Now we know that the same applies to MM. In all likelihood, this will also hold true for other types of cancer,” said De Keersmaecker. “Our next research goal is finding out for which cancers this is the case, how the link between ribosome and proteasome works, and what the possibilities are of drugs that target the ribosome itself,” she said.
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