The study results provide data linking genetic events in ALL taken from patients when first diagnosed to their future clinical survival. In the lab, the researchers reproduced human ALL in mice transplanted with patient leukemia samples. Sometimes the dominant genetic family would grow in the mice while in other mice the rarer families would grow.
"By looking at the genetic signatures of the leukemia cells in the different mice we were able to figure out their genetic ancestry and the evolutionary trajectory that that particular leukemia took. We found that if a particular gene family was mutated, the tumours were aggressive when grown in the mice. The patients with the corresponding tumours had poorer survival showing that the human-mouse transplant system could be very useful in predicting patient outcome."
This insight into genetic diversity has positive implications for cancer treatment, says Dr. Dick. "Understanding the complexity of cellular relationships and the existence of distinct genetic families of leukemia cells will shed light on why some cells of the cancer are not killed by the therapy and eventually regrow resulting in disease relapse, and help accelerate the development of tailored therapies to wipe out all the unwanted branches in the genetic tree."
Research collaborator Dr. Charles Mullighan, a hematologist at St. Jude Children's Research Hospital, adds: "Overall, the study proved that many leukemias comprise multiple subpopulations with different genetic alterations, and that these genetic alterations may evolve over time. The main clinical implication is that we now need to extend this work to identify genetic changes at low levels at diagnosis that confer a high risk of treatment failure and relapse and find ways of targeting them."
The current research builds from earlier
|Contact: Jane Finlayson|
University Health Network