Discovery of a rare stem cell as the likely origin of malignant multiple myeloma cells may lead to treatments that can produce a long-term cure, according to an article published online December 4th by the journal Blood.

The American team had begun research to learn why multiple myeloma recurs so frequently by studying bone marrow malignant plasma cells and normal B-cells; the stem cell is found only in 1 of every 10,000 cells or less than 1 percent of all myeloma cells.

Current treatments targeting malignant plasma cells may not be effective on the abnormal stem cells, allowing the disease 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, MD, senior investigator of the study. "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 coauthor William Matsui, MD.

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," said Matsui.

"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."

The research team is currently testing therapies including antibodies that target the stem cells and drugs to make them differentiate prematurely. Cancer stem cells have already been identified as the origin of malignant cells 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.