Leukaemia cells run but don't hide

An Anglo-Australian team of researchers has pioneered a new method of zooming in on leukaemia cells in action and found that the notoriously treatment-resistant blood cancer cells are not playing ‘hide and seek’, as was traditionally believed, but are actually playing a game of ‘tag’.

Adult leukaemia patients typically suffer a 50% relapse rate after initial chemotherapy. Subsequent treatments tend to be less effective, resulting in a fatal spreading of the cancer. An international team of researchers, led by Dr Edwin Hawkins from Melbourne’s Walter and Eliza Hall Institute of Medical Research (WEHI), has determined that the long-held hypothesis of acute lymphoblastic leukaemia (ALL) cells hibernating in bone marrow to avoid cancer treatments is inaccurate.

In collaboration with Dr Cristina Lo Celso from Imperial College London, Dr Hawkins’ team found that the cancerous cells which evade chemotherapy are not hiding or hibernating but running away.

“We realised that instead of playing hide and seek with the chemotherapy, as was initially thought, the treatment-resistant ALL cells were engaging in a ‘catch me if you can’ game of tag,” Dr Hawkins said. “Right before our eyes, these cells were sprinting off in all directions: dividing, jumping in and out of blood vessels and using such ‘highways’ in the body to migrate and recolonise.”

Pioneering a high-resolution technique likened to a cellular equivalent of CCTV, the team were able to create ‘optical windows’ allowing them to zoom in to the level of a single micron. Previous analysis only gave researchers static snapshots at this level of magnification, but the new system is closer to a video feed of cellular-level activity.

Dr Hawkins said, “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.”

This dynamic new perspective will lead to a paradigm shift in tailoring treatments for ALL patients. Dr Hawkins said, “We now know that it is ineffective to design treatments to target the surrounding stromal cells or ‘hiding places’ of the cancer, because the cells are not hiding.”

Another benefit of being able to observe cancer cells in action at this level is developing new pain treatments. Co-author Dr Delfim Duarte of Imperial College London said, “We also discovered that pain experienced by many leukaemia patients is caused by cells stripping and destroying tissue lining the bone, rather than overcrowding and causing pressure.”

Dr Hawkins is confident that this new discovery will revolutionise the way this particular form of cancer is treated. He said, “To beat leukaemia, we must develop a treatment that targets the ability of the cells themselves to ‘run’ around the body. We are now working on finding a way to stop these cells in their tracks and win the game of tag.”

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

Image courtesy of Erik Schmidt under CC BY-NC 2.0