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Cancer stem cells for multiple myeloma resist to treatments


Researchers at the Johns Hopkins Kimmel Cancer Center have shown that cancer stem cells for multiple myeloma share many properties with normal stem cells and have multiple ways of resisting chemotherapy and other treatments.

A report on the evidence has been published in the journal Cancer Research.

The existence of cancer stem cells - a topic of some controversy in cancer biology - is seen by some scientists as a useful explanation for the long history of difficulty in overcoming some cancers’ persistence.

The Hopkins investigators previously had uncovered a rare stem cell in myeloma, accounting for less than one percent of all the cancer’s cells. Working with cell samples from myeloma patients, the team found that this stem cell originates from immune system B-cells and is capable of giving rise to the malignant bone marrow cells characteristic of the disease.

In the current study, the Researchers isolated stem cells from the blood of four patients with multiple myeloma and transplanted them into mice. All of the animals developed hind-limb paralysis and showed signs of cancer in the bone marrow. By contrast, plasma cells that were transplanted from multiple myeloma patients to mice did not engraft. Recreating the disease in mice provides more evidence that these cells act as cancer stem cells.

The Johns Hopkins Researchers also compared the response of these special stem cells with the bulk of multiple myeloma plasma cells, to four different chemotherapy medications commonly used to treat patients with the disease: Dexamethasone, Lenadilomide, Bortezomib and 4-Hydroxycyclophosphamide. While all four agents significantly inhibited the growth of the plasma cells, none inhibited the stem cells.

To their surprise, the research team noted that the multiple myeloma stem cells resemble other types of adult stem cells and exhibit similar properties that may make them resistant to chemotherapy. They found that the stem cells contain high levels of enzymes that neutralize toxins, like cancer drugs, and expel them through miniature pumps on their cell surface. The Researchers believe that these drug-fighting enzymes and pumps - also plentiful in normal stem cells - may help cancer stem cells resist treatment.

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.

Source: Johns Hopkins Medical Institutions, 2008

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