After a chance observation while doing laboratory experiments, researchers at the Stanford University School of Medicine have found a method for forcing dangerous human leukaemia cells to change into harmless immune cells known as macrophages.
Macrophages are specialized type of white blood cells that engulfs and digests cellular debris, foreign substances, microbes, and cancer cells in a process called phagocytosis.
The researchers were experimenting on a human B-cell acute lymphoblastic leukaemia with a mutation called the Philadelphia chromosome obtained from a patient. Accordingly, this type of cancer cells causes a very aggressive form of leukemia with no known effective cure.
In an attempt to keep the cells alive in a culture plate to further their study, the researchers tried several approaches.
“We were throwing everything at them to help them survive,” said Ravi Majeti, MD, PhD, senior author, assistant professor of medicine at Stanford, and member of the Stanford Cancer Institute and Stanford Institute for Stem Cell Biology and Regenerative Medicine.
Scott McClellan, MD, PhD, lead author of the paper and postdoctoral scholar, said that some of the cells in culture transformed into what appeared to be macrophages. The entire research team concurred to the observation but they were wondering how the supposed cancer cells changed into harmless immune cells.
Eventually, Majeti remembered an earlier study that showed how mouse progenitor B-cells could transform into macrophages by force through exposure to certain transcription factors or proteins that bind to particular DNA sequences.
The researchers reiterated that B-cells are progenitor cells. They are cancerous because they stay in an immature state. From this understanding, the researchers carried more experiments and observations. They subsequently confirmed that the study involving the mouse progenitor B-cells is also suitable to transform the human cancer cells into macrophages.
A key takeaway from this study is that apart from neutralizing the extremely dangerous B-cells by transforming them into harmless and immune-boosting macrophages, it also presents new hopes for curing the particular type of leukemia caused by the cancer cells.
“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,” Majeti said.
The researchers will further expand the study. Their next step is to find a drug that would trigger the same reaction or transformation, thus finding a new therapy for treating leukemia.
Further findings are detailed in a paper published in the journal Proceedings of the National Academy of Sciences. Other Stanford co-authors of the paper are computational biologist Andrew Gentles, PhD, and technician Christine Ryan, who is now a medical student at Stanford. Photo credit: Adapted/CC-SA