Origin of multiple myeloma found in rare stem cell

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 one 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,” explains Richard Jones, M.D., professor and 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,” says William Matsui, M.D., assistant professor of oncology at the Johns Hopkins Kimmel Cancer Center.

They 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,” says 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.”

Therapies for myeloma undergoing study at the Johns Hopkins 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 from the Johns Hopkins Kimmel Cancer Center.

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