Scientists have long wondered how some leukemia cells are able to so effectively evade the forces of chemotherapy to pop up again after multiple treatments. One of the leading schools of thought was that they take cover in the bone marrow while the chemical storm passes, but new research has flipped this on its head. Using an advanced imaging technique, scientists have watched as treatment-resistant leukemia cells teased chemotherapy into a high-stakes game of tag, an observation that opens up new ways in which we may be able to stop the deadly disease in its tracks.
Because leukemia is cancer of the blood, chemotherapy stands as the primary form of treatment. This involves injecting drugs or administering them orally, which then travel throughout the bloodstream to attack the cancer cells all over the body. While this often results in the destruction of most of the cancer cells, the disease only requires some of them to resist the treatment to be able to spread and become fatal, which scientists have suspected they may do by hiding away in the bone marrow.
Scientists at the Walter and Eliza Hall Institute and London's Imperial College set out to explore the interplay between acute lymphoblastic leukemia (ALL) cells and their surrounding environment in a mouse model. They did this using a form of intravital microscopy, a technique used to observe cellular behavior within living tissue. But where previous intravital microscopy technologies offered scientists only static snapshots, the team's new version offers optical windows displaying high-resolution video, likened to CCTV for cellular behavior.
"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 (0.13 x 0.1 in), right down to a single micron – it's incredible," said the Walter and Eliza Hall Institute's Dr. Edwin Hawkins.
Using this new tool to watch the cancer cells in action, the researchers discovered how rather than concealing themselves in the bone marrow in response to chemotherapy, they actually drew the chemotherapy into a "catch-me-if-you-can" type 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 recolonize," Dr. Hawkins said.
This new perspective on cancer could have a number of implications. For now, the scientists say it shows that the pain a lot of leukemia victims feel is caused by the cells destroying tissue in the bone lining, rather than overcrowding it as previously thought. Further to that, it will allow scientists to better direct their research efforts in coming up with better treatments.
"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," said Dr. Lo Celso from London's Imperial College. "To beat leukemia, 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.'"
You can hear from Dr. Hawkins in the video below, and the team's research was published in the journal Nature.
Source: Walter and Eliza Hall Institute
