A chance observation in a lab at Stanford University has led to the discovery of a novel new method that can convert leukaemia cells into macrophages – harmless cells central to the immune system.
B-cell acute lymphoblastic leukaemia is a particularly aggressive form of cancer and therefore has typically poor outcomes. This new discovery marks the potential for a new treatment that could help fight the continuing battle against cancer.
The finding was made when Dr Scott McClellan, one of the lead authors of the paper, noted that some cultured cells were beginning to change shape and size into something that resembled macrophages. When early B-cell progenitor cells are exposed to certain transcription factors (proteins involved in the processing of DNA) they can be forced to become macrophages.
Dr Ravi Majeti, senior author, explained: “B-cell leukaemia cells are in many ways progenitor cells that are forced to stay in an immature state.” Student and another lead author, Christopher Dove, performed several more experiments to confirm that the same methods that had been previously used to transform mouse progenitor cells could be used to transform the cancer cells. “We put signalling molecules on the outside of some leukaemia cells, and this told the inside of the cell to stop behaving like cancer and start behaving like a useful immune cell,” he said.
The use of primary cells in the research is promising, as these cells are extracted from real cancers and so are the closest models available for the disease. It is, however, important to note that this is a preclinical study. The next steps are to search for a drug that can stimulate a same reaction – something that would be a promising basis for a new therapy. Retinoic acid is a well-established treatment used to transform cancer cells into mature granulocytes, so there is clear precedent for such a treatment. Majeti is optimistic for the future. “There’s a big-time interest in differentiation therapies for cancer” he said.