FORCING leukaemia cells to “grow up” and behave responsibly has been shown to tame the disease in the laboratory.
SCIENTISTS hope the discovery will lead to radical new treatments for the blood disease and possibly other kinds of cancer.
A hallmark of all cancer cells is that they are immature, or “undifferentiated”. In a new study, researchers genetically reprogrammed leukaemia cells so they grew to resemble ordinary white blood cells. The cancer cells took on the appearance of “macrophages”, immune system cells that engulf and consume dead and cancerous cells, as well as invading microbes. Laboratory mice that had the altered cells transplanted into them remained healthy. The US scientists believe the rehabilitated leukaemia cells could end up helping to fight the cancer they were once part of. They are looking for a drug that can perform the same trick and reprogram leukaemia cells in humans. The experiments were conducted with cells taken from a patient with B-cell acute lymphoblastic leukaemia (B-ALL) containing a genetic a mutation called BCR-ABL1 plus. This is an especially aggressive form of leukaemia, associated with a poor prognosis. The scientists, led by Dr Ravi Majeti, from Stanford University in California, wrote in the journal Proceedings of the National Academy of Sciences: “Together, our findings establish a rationale for exploiting … reprogramming as a therapeutic strategy in BCR-ABL1 plus B-ALL.” Reprogramming was achieved by exposing the leukaemia cells to certain molecules – cell-signalling cytokines and a particular transcription factor protein – that altered the activity of their genes. “The resultant cells resembled normal macrophages in appearance, immunophenotype, gene expression, and function,” the researchers wrote. “Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts.” The next step will be to find a “differentiation drug” that can serve as the basis of a practical therapy for leukaemia. There is already a precedent for such a treatment, say the researchers. Retinoic acid, derived from vitamin A, is used to treat another blood cancer, acute promyelocytic leukaemia, by turning cancer cells into mature cells called granulocytes. So far this is the only well-established therapy that matures cancer cells, but experts hope to find more. “There’s big-time interest in differentiation therapies for cancer,” Dr Majeti added.