Toronto: In what could lead to the development of new cancer therapies, scientists have discovered that defective genes and individual leukaemia cells that carry them are organised in a more complex way than previously thought.
The findings published today in journal Nature challenge the conventional scientific view that cancer progresses as a linear series of genetic events and that all the cells in a tumour share the same genetic abnormalities and the same
growth properties.
"Our results show this is not the case and open the way to discover how genetic abnormalities transform normal cells into leukemic cells," said Dr John Dick at the Ontario Cancer Institute (OCI) in Canada.
The findings also show "how leukemic cells at different steps of genetic evolution (or progression) respond to therapy, or contribute to relapse," said Dr Dick, who is also the director of the Cancer Stem Cell Program at the Ontario
Institute for Cancer Research.
The research team found that the leukaemia cells taken from patients with acute lymphoblastic leukaemia (ALL) are actually composed of multiple families of genetically distinct leukaemia cells.
They looked at how these families developed and retraced the ALL 'family tree' back to its origins. They discovered that the so-called black sheep - the cells that propagate the disease and potentially survive therapy - persist through
generations, and even branch off and evolve to form genetically distinct cancer families.
Some of these genetic families dominate, making it appear that the leukaemia cells only have one set of genetic abnormalities while other families are very rare, explaining why they had never been seen before.
The study provides 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 leukaemia 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 leukaemia cells in the different mice we were able to figure out their genetic ancestry and the evolutionary trajectory that that particular leukaemia took," said Dr Dick.
"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."
According to the researcher, this insight into genetic diversity has positive implications for cancer treatment.
"This will help accelerate the development of tailored therapies to wipe out all the unwanted branches in the genetic tree," said Dr Dick.
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