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Blood cancers shown to arise from mutations that accumulate in stem cells

How and why do some cells in our bodies become cancerous?  Can any cell become cancerous, or only certain kinds of cells? Those are longstanding questions with big implications for treating and preventing cancer.

In the case of leukemias, Stanford researchers finally have an answer to the first question: Mutations accumulate slowly in blood stem cells, the cells that produce all the cells of the blood and immune system. This had been a controversial theory of some experts, and the team proved it correct by comparing mutations found in leukemia cells with mutations found in blood stem cells from the same patient. As I explain in a release today:

When the researchers compared mutations in these seemingly normal blood stem cells with the leukemia cells, they could reconstruct exactly which mutations led to the leukemia, and the order in which the mutations arose. They did this by looking for blood-forming stem cells with a single mutation, which they knew must be the first, then finding other stem cells with that first mutation plus one other, which they could then identify as the second. They continued to do this until they found examples of stem cells at each stage of mutation accumulation, leading up to the full set of mutations found in the actual leukemia cell.

Individual mutations can occur in mature blood and immune cells too, but these cells will die off naturally before they get the whole set of mutations needed to cause cancer. Only the stem cells, which last a lifetime, are around long enough to accumulate all the mutations.

This information is important for treating leukemia (and perhaps other cancers, if the same pattern applies). Leukemia can initially be treated with chemotherapy to kill the cancer cells, but patients will often relapse - the cancer comes back, often more deadly than before. One possibility is that relapse occurs because a few leukemia cells survived the chemotherapy, in which case the solution might be increase the potency of the chemotherapy. But if relapse occurs because the stem cells are creating new leukemia cells, then it really won’t matter how effective chemotherapy is because the mutated stem cells are acting as a reservoir for the disease. Co-principal author Ravi Majeti, MD, PhD, said this area will be the focus of the next phase of the team's research.

This study appears in Science Translational Medicine.

Previously: Leukemia prognosis and cancer stem cells

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