The longstanding question of how leukaemia survives chemotherapy has been answered by researchers in Australia and the United Kingdom, bringing the world closer to more effective therapies for this devastating cancer.

Leukaemia is a cancer of the blood with significantly high mortality rates. In Australia, 50% of adult leukaemia patients relapse after their initial chemotherapy treatment. Often resistant to subsequent treatments, the cancer spreads and becomes fatal.

Published in Nature, research led by Dr Edwin Hawkins from Melbourne’s Walter and Eliza Hall Institute and Dr Cristina Lo Celso from London’s Imperial College, has overturned popular theory that acute lymphoblastic leukaemia (ALL) cells resist cancer treatment by hiding in bone marrow.

Dr Hawkins said findings revealed that while chemotherapy was able to eliminate the majority of cancerous cells, the remaining treatment-resistant cells were doing the exact opposite of ‘hiding’ in order to survive.

“It was a surprising twist. We realised that instead of playing ‘hide-and-seek’ with the chemotherapy, the treatment-resistant ALL cells were engaging in a ‘catch-me-if–you-can’ game of ‘tag’.

"Right before our eyes, these cells were sprinting off in all directions: dividing, jumping in and out of blood vessels and using such ‘highways’ to migrate and recolonise,” Dr Hawkins said.

To capture this remarkable action, the researchers had developed a revolutionary high-resolution technique using ‘optical windows’ which, for the first time ever, enabled the cellular equivalent of CCTV-like observation.

Dr Hawkins said previous techniques only involved analysis of static snap-shots, rather than any kind of video-based medium.

"Our new technique allows us to watch action unfolding for days, with the ability to zoom in and out on the same patch of tissue: from 3.5 x 2.5 mm, right down to a single micron – it’s incredible,” he said.

Dr Lo Celso said this dynamic new perspective would mean a shift in focus for researchers working to advance treatments for ALL.

“We now know that it is ineffective to design a treatment to target the surrounding stromal cells or ‘hiding places’, because the cancer cells are not hiding,” Dr Lo Celso said.

“To beat leukaemia, we must instead develop a treatment that targets the ability of the cells themselves to ‘run’ around the body. Researchers must find a way to stop these cells in their tracks and 'win the game of tag',” she said.

Study co-author Dr Delfim Duarte, also from Imperial College, said there was much to learn by being able to observe cancer in this way.

“We also discovered that pain experienced by many leukaemia patients is caused by cells stripping and destroying tissue lining the bone, rather than from pressure caused by cells over-crowding as was initially thought. We have much to gain from this dynamic new information source, ” Dr Duarte said.

The research was funded by Australia’s National Health and Medical Research Council (NHMRC), charities Bloodwise and Cancer Research UK, the European Research Council, the Human Frontier Science Program, and the European Hematology Association.

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