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
20 to 40% of the patients with multiple myeloma - a type of
leukemia - have a defect in the ribosome, the protein factory of the
cell. These patients have a poorer prognosis than patients with intact
ribosomes. At the same time, they respond better to a drug that already
exists. These are the findings of a study by the Laboratory for Disease
Mechanisms in Cancer at KU Leuven (University of Leuven), Belgium.
‘Multiple myeloma patients with a defect in the ribosome have a poorer prognosis. At the same time, they respond better to a drug (proteasome inhibitors) that already exists.’
Doctoral student Isabel Hofman (KU Leuven) discovered defects in the
ribosome of MM patients. "The ribosome is the protein factory of a
cell. In MM patients, one part of the ribosome is produced less in 20 to
40% of the patients, depending on how aggressive the cancer is.
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,"
explains Professor 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. 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. In other words, their poorer prognosis can be
offset by this treatment. 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."
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 leukaemia. Now
we know that the same applies to MM. In all likelihood, this will also
hold true for other types of cancer. 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."