Science - A new cancer model

For first time, scientists observe how leukemia evolves

UW study could lead to doctors finding out why drugs fail in treating some cancer cells

Scientists in Madison have sent blood cells from a leukemia patient back to the embryonic state for the first time, opening a window into the early development of the disease and raising the possibility that doctors may come to understand why existing drugs do not appear to work on a powerful subset of cancer cells.

"We have now very good drugs for leukemia treatment. Most drugs kill more mature leukemia cells, but there are some cells, cancer stem cells, that this drug cannot kill," said Igor I. Slukvin, an associate professor of pathology at the University of Wisconsin-Madison and one of the authors of the new study published this week in the journal Blood.

The effort to watch leukemia develop could shed new light on the theory that cancer includes a relatively small population of insidious stem cells that trigger tumors and resist chemotherapy. If true, the cancer stem cell theory would expose the futility of some current treatments, suggesting that patients are receiving powerful drugs that fail to kill the crucial cells. The theory could also refocus cancer research.

"This makes a new in vitro model," said Nady Golestaneh, assistant professor of biochemistry and molecular and cellular biology at Georgetown University Medical Center. "I think it's a big step toward making research progress."

Golestaneh did not work on the UW study.

Using human cell reprogramming technology first pioneered by his UW colleague James Thomson and by Shinya Yamanaka at Kyoto University, Slukvin and his colleagues spent a year and a half to two years on the effort to send leukemia blood cells back to the embryonic state. Once back, the cells can now be grown in a lab dish to become blood cells once again, allowing scientists to observe their evolution into cancer.

In the second phase of the project, Slukvin said, researchers plan to inject the leukemia blood cells into mice in hopes of finding among them the deadly subset of cancer stem cells.

If they can identify these cells, scientists can try killing them with different drugs.

The effort to find and eradicate cancer stem cells is likely to include many labs around the country. Slukvin said he plans to make the reprogrammed leukemia blood cells available to other researchers.

Parameswaran Hari, a medical oncologist specializing in blood cancers at Froedtert Hospital in Wauwatosa, said the new study will help researchers develop new drugs to treat leukemia. He said many drugs treat the disease and, often, they can send it into remission.

Yet the cancer comes back.

"Most of our drugs only kill dividing (cancer) cells," said Hari, who directs the adult blood and marrow transplant program at Froedtert. "We are not good at eradicating stem cells."

The new paper is notable also for the reprogramming technique that was used. Instead of using viruses to ferry special reprogramming genes into the cells as scientists did a few years ago, Slukvin and his colleagues used a newer method developed by Thomson. They used plasmids - small, very stable circles of DNA, which can deliver reprogramming genes without leaving behind viruses and other material that can cause health problems.

The reprogramming of leukemia blood cells continues a trend that began when Thomson and Yamanaka first announced the reprogramming of human skin cells in 2007. Both scientists realized that the breakthrough would make it possible for researchers to watch diseases attack cells in a lab dish.

Since then scientists have used the technique to study spinal muscular atrophy, Lou Gehrig's disease and other ailments.

George Daley, a stem cell researcher at Children's Hospital Boston and the Harvard Medical School, praised the new work at UW saying it creates "a very clever cancer model, which previously hasn't been possible."