Johns Hopkins
Kimmel
Cancer Center scientists have identified the cell
likely to be responsible for the development of multiple
myeloma, a cancer of the bone marrow that destroys bone
tissue. The research, published in Blood online,
suggests that therapies designed for long-term cure of the
disease should target this stem cell, which, unlike other
cells, can copy itself and differentiate into one or more
specialized cell types.
In their studies to learn why multiple myeloma so
often recurs following drug treatment, the investigators
uncovered a rare stem cell, occurring in just one out of
every 10,000 cells, or less than 1 percent of all myeloma
cells.
Working with immune system B-cells, the Johns Hopkins
team found that this stem cell gives rise to the malignant
bone marrow plasma cells characterized by multiple
myeloma.
Current treatments target the malignant plasma cells
but may not be effective on the errant multiple myeloma
stem cells, allowing the cancer to recur. "Most therapies
today are aimed at the cancer you can see, but to cure
cancer you have to go after the cells responsible for the
disease, similar to how we kill a weed by getting at its
roots, not just the part above the ground," explained
Richard Jones, director of bone marrow transplant at the
Johns Hopkins Kimmel Cancer Center. "If you cut off the
flower and stem of a dandelion, it may look like it has
died for a period of time, but the weed eventually will
grow back. If you get the root, however, the weed does not
grow back."
The scientists found the rare stem cell by looking at
markers on the surface of damaged B-cells, which develop
into plasma cells that cannot divide and multiply. "We know
what the markers are on cancerous plasma cells and the
antibodies they make, and we also know the markers on
B-cells that are not cancerous. So, we went looking for a
B-cell that has the same antibodies, can make copies of
itself and mature into cancerous plasma cells," said
William Matsui, assistant professor of oncology at the
Johns Hopkins Kimmel Cancer Center.
The researchers found that this multiple myeloma stem
cell looks and acts genetically different from the plasma
cell.
"Because these two cells are biologically different,
we may need two therapies — one to kill the plasma
cells, or the visible part of the weed, and one to kill the
root, the stem cells," Matsui said. "Treatments that are
directed at myeloma plasma cells are likely to produce
visible results, but they will be temporary improvements
unless we also target the myeloma stem cell."
Therapies for myeloma undergoing study at the Kimmel
Cancer Center include antibodies that target the stem cells
and drugs to make them age prematurely. Cancer stem cells
have been found as the culprit in chronic myeloid leukemia,
and the scientists believe the same pattern of cancer
development may apply to other cancers, including breast
cancer, acute myeloid leukemia and acute lymphocytic
leukemia.
Multiple myeloma is the second most common blood
cancer and strikes more than 14,000 Americans each year.
Close to 11,000 will die from the disease.
This research was funded by the National Cancer
Institute.
Other participants in this research include Carol Ann
Huff, Qiuju Wang, Matthew T. Malehorn, James Barber, Yvette
Tanhehco, B. Douglas Smith and Curt I. Civin, all from the
Johns Hopkins Kimmel Cancer Center.
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