Mapping Leukemia Evolution

Leukemia genetic lineages show chemotherapy resistant stem cells responsible for remission

(RxWiki News) The thing that strikes the most fear in the hearts of cancer patients is wondering if a remission is real, or if the cancer is just on pause. These fears linger despite the most aggressive treatments and the best doctors.

Applying mathematics to cellular biology, a group of scientists in Israel reconstructed the genetics of leukemia mutations, attempting to map out the precise genetic changes responsible for chemotherapy failure.

"Ask your oncologist about remission."

Ehud Shapiro, PhD, professor at the Weizmann Institute, led the team that mathematically retraced the pattern of mutations back to the original cells, finding that the lowest common denominator was the highly resistant stem cells at the very beginning of the path from normal cell to leukemia.

Dr. Shapiro's team concluded that at least in some of the patients, these early cancer cells did not divide often.

This slow growth was responsible both for the significant resistance to chemotherapy in these cells, and is the reason that leukemia and other cancers may take months or years to produce symptoms or resurface after treatment.

Chemotherapy, radiation and other forms of general cancer treatment are most effective at killing cells that are dividing at that time.

This is effective in killing 90-95 percent of cancer cells, which typically are dividing or growing all of the time, unlike most normal healthy human cells.

Earlier studies have found that several treatments can kill up to 99 percent of all cancer cells, but given enough time, the remaining cells may be able to avoid the body's natural defenses against cancer and resurface.

This time in between detectable active cancer growth is called remission, and it is difficult to predict how long it will last.

Researchers compared two different blood samples from leukemia patients. They took blood from newly diagnosed leukemia cancer patients and then compared the results with blood samples taken after chemotherapy, when the leukemia returned.

Mathematical techniques pioneered by Dr. Shapiro's team were able to pinpoint the genetic lineages of the cancers back to a common ancestor stem cells for both samples.

Dr. Shapiro stated the findings of his research and the implications for the developing more effective cancer treatments.

"We know that in many cases, chemotherapy alone is not able to cure leukemia. Our results suggest that to completely eliminate it, we must look for a treatment that will not only eliminate the rapidly dividing cells, but also target the cancer stem cells that are resistant to conventional treatment."

The study was published in the journal Blood on May 29, 2012.

The research was funded by several nonprofit foundations as well as the European Research Council.

Review Date: 
June 1, 2012