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Stanford researchers deliver double punch to blood cancer

Acute myeloid leukemia is an aggressive and deadly cancer affecting cells that turn into our blood. Now, a study published in Nature Medicine shows that a drug known to cause cell death might be effective for a particular subtype of this lethal disease.

To get an idea of just how aggressive and deadly acute myeloid leukemia is, consider the survival rates for the 13-14,000 American adults who are sickened each year. The overall survival rate is 30-40 percent, according to Stanford cancer researcher Ravindra Majeti, MD, PhD, but if patients are over 65 years old, the survival rate dips to just 5 percent. The majority of acute myeloid leukemia patients are elderly.

Apoptosis, or cell death, of tumors is the goal in cancer treatments. There are multiple pathways leading to cell death, and identifying ways to nudge cancer cells towards dying is the focus of much cancer research.

But sometimes the path to cell death is nonlinear and hard to find.

In this work, a team of Stanford cancer researchers led by Majeti and Steven Chan, MD, identified a two-pronged attack for acute myeloid leukemia cancer cells. The researchers first focused on mutated proteins called isocitrate dehydrogenase 1 and 2 (known as IDH1/2 for short). Cancer cells containing mutated IDH1/2 proteins often survive traditional chemotherapy treatments, contributing to relapse, and they exist in 15 percent of acute myeloid leukemia patients. The second focus of the Stanford researchers was the BCL-2 gene, which is known to enable cancerous growth by putting the brakes on cell death in acute myeloid leukemia and other cancer cells. Simply stopping BCL-2 activity in acute myeloid leukemia patients is not very effective, as indicated by low survival rates for the disease.

The Stanford scientists found that giving a drug that inhibits BCL-2 successfully lifted the blockade on cell death, but only in cells with mutated IDH1/2 proteins. Majeti said the drug that promotes cancer cell death by inhibiting BCL-2 is now in clinical trials.

Kimberlee D'Ardenne is a writing intern in the medical school's Office of Communication and Public Affairs.

Previously: The latest on stem-cell therapies for leukemia, Blood cancers shown to arise from mutations that accumulate in stem cells and Leukemia prognosis and cancer stem cells

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