‘Chameleon cancers’ avoid treatment by changing colors and identity

Researchers discovered a method that explains how certain types of leukemia attempt to avoid treatment by changing their appearance and identity.

The specific blood cancers

The researchers from the University of Birmingham and Newcastle University in the U.K., and the Princess Máxima Center in The Netherlands, examined the responses of children undergoing therapy for blood cancer treatment.

The study was published in the journal Blood.

There have been huge improvements and discoveries in treating blood cancers over the last 50 years, with 90% of children being cured from the blood cancer acute lymphoblastic leukemia (ALL).

However, while treating the blood cancer, doctors have realized that some forms of leukemia do not respond to treatment. For the patients who do not respond to treatment options, researchers are still working on new immunotherapies, like cell-based treatments, such as CAR T-cells.

Some leukemias can evade immunotherapies by stopping the production of cell proteins that the therapy targets.

Other leukemias switch to become a completely different kind of blood cancer, causing the therapies to stop working. Researchers discovered a specific gene called the MLL gene that creates a higher risk of the cancer returning in patients.

How do 'chameleon cancers' change?

The research team discovered the cause of ‘chameleon cancers.’ They revealed the mechanism that explains how these cancers change their appearance and identity.

The team examined tumorous DNA of twelve children and adults with ALL, whose cancer showed the change in the MLL gene. They noticed that on-off switches were changed.

“ALL cells carrying this chromosomal rearrangement have long been known to be able to relapse as a different type of blood cancer, acute myeloid leukemia (AML). By studying these switched MLL/AF4 leukemias we showed that the switch can happen in blood cells throughout different stages of development in the bone marrow,” said Dr Simon Bomken, co-lead author of the study and MRC Clinician Scientist and Honorary Consultant at Newcastle University.

The co-lead author also mentioned how the on-off switch occurs in blood cells during various stages of development in the bone marrow. The switch can be a result of additional genetic changes from chemotherapy as well. This can cause some types of leukemia to “re-programme themselves and switch identity from one cell type to another.”

Difficulty in treating 'chameleon cancers'

If the ALL cells do change their identity, they are more difficult to treat. Dr. Olaf Heidenreich, co-lead author and research group leader at the Princess Máxima Center for pediatric oncology, stated “Our new research will help us in the future to pick out those children with leukemia who are at greatest risk of their cancer coming back, so we can adjust and personalize their treatment.” Each year, approximately 110 children are diagnosed with the blood cancer ALL in The Netherlands.

“The fact that we now understand what the drivers of this switch are has important implications for our understanding of disease development,” Heidenreich said.

The researchers want to use this study to eventually prevent any switches by blood cancer cells and stop the leukemia from changing its identity, making the treatments as effective as possible.