B-ALL is an aggressive cancer that affects white blood cells.
They report how they discovered it is possible to reprogram cancerous white blood cells to mature into harmless immune cells in the Proceedings of the National Academy of Sciences.
Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive cancer that affects a type of white blood cell. The cells are immature B cells that are unable to fully differentiate into normal B cells.
In their study, the researchers show how they reprogrammed cancerous cells from B-ALL patients to transform into cells that resemble normal immune system cells called macrophages that do things normal macrophages do - like gobble up bacteria.
Moreover, the team showed that unlike typical B-ALL cells, the reprogrammed cells did not cause disease in mice with weakened immune systems.
And they also showed it is possible - to some extent - to reprogram cells in B-ALL patients, suggesting the method offers a route for investigating previously unidentified treatments.
Chance discovery that B-ALL cancer cells can be reprogrammed into harmless cells
Senior author Ravi Majeti, an assistant professor of medicine at Stanford, says they made the discovery after collecting leukemia cells from a patient and were back in the lab trying to keep the cells alive in culture: "We were throwing everything at them to help them survive," he adds.
As they continued with their attempts, one of the team noticed that some of the cancer cells in the culture were undergoing physical transformation. They observed that the cells' shape and size changed and they began to resemble macrophages - literally "big eater" scavenger cells of the immune system that go around gobbling up waste material and undesirable pathogens like bacteria.
Prof. Majeti then remembered an old paper that showed how in mice, precursor versions of B-cells can be forced to become macrophages when exposed to certain transcription factors - proteins that bind to DNA and help to translate the genetic code into RNA for making proteins and instructing cells what to do. He explains:
"B-cell leukemia cells are in many ways progenitor cells that are forced to stay in an immature state."
So in their study they carried out further experiments and found that what had been shown possible in mice in the old paper could also be made to happen in human cells: with the help of transcription factors, they converted the B-ALL cancer cells into harmless macrophages.
Big interest in 'differentiation therapy' to treat cancer
The team says there is reason to believe that the method not only renders the cancer cells harmless, but in their new state the cells may even be recruited to fight cancer. One of the jobs that macrophages undertake is to present other cells in the immune system with recognizable bits of faulty cells - including cancer cells, as Prof. Majeti explains:
"Because the macrophage cells came from the cancer cells, they will already carry with them the chemical signals that will identify the cancer cells, making an immune attack against the cancer more likely."
The team now plans to find a drug that triggers the same reaction that can then be developed into a treatment for leukemia.
They are hopeful because there is a precedent - acute promyelocytic leukemia can be treated with retinoic acid, which transforms the cancer cells into mature cells called granulocytes.
That treatment is an example of an exciting new development in cancer therapy called "differentiation therapy," that uses cell differentiation as a way to neutralize cancer cells. There are many teams around the world now working on this, says Prof. Majeti:
"There's big-time interest in differentiation therapies for cancer."
The study was funded by the National Institutes of Health (NIH), the New York Stem Cell Foundation, the Burroughs Wellcome Fund, the US Department of Defense and the Walter V. and Idun Berry Postdoctoral Fellowship Program.
In January 2015, Medical News Today reported a study where researchers discovered that acute myeloid leukemia may arise from an interaction between two molecules. They suggest the pathway could be a potential target for the treatment of the aggressive blood cancer, and that one of the molecules could serve as a biomarker to deliver personalized therapy to patients with the disease.