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Coaxing leukemia cells into an embryonic state

A team of researchers led by Ludwig Stanford’s Ravi Majeti have figured out how to push a human leukemia cell back into to a nearly embryonic state as an induced pluripotent stem (iPS) cell. Over the past 10 years, researchers around the world have routinely reverted a variety of mature cells into iPS cells, but no one has yet pulled off the feat with leukemia cells. Majeti and his colleagues added a few of their own biochemical tricks to the procedure to do so, and examined how the cells would behave when prodded to mature along different paths. Their findings were published online today in Cell Stem Cell.

The researchers report that when they grew the leukemia iPS cells up into other kinds of tissue like heart cells or neurons, the cells behaved normally. But when they grew them back to be blood cells, they once again became cancerous. “This was super surprising to us,” says Majeti, who is an investigator at the Ludwig Center at Stanford. “What this tells us is that context matters. Those leukemic gene mutations only cause cancer when they exist in the context of a blood cell.” The ability to generate iPS cells from a single leukemia cell will help researchers study the natural variations that occur among leukemia cells. They could, for example, use this approach to create and study the leukemia generated by each subclone in a patient’s cancer.

This could help improve how physicians treat the disease. For example, pure populations of various subclones from a leukemia patient could be grown and tested to see how each responds to different drug therapies. If, say, one subclone is less affected by a therapy than others, that may set the patient up for a relapse following treatment. Indeed, by analyzing blood samples stored over the course of one patient’s treatment, the researchers show that one subclone isolated from the samples was more resistant to chemotherapy. This subclone turned out to be the source of that patient’s eventual relapse.

Majeti is also an Associate Professor at Stanford.


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