Targeted Attack on Leukemia

One of the most common, and least treatable, adult leukemias could be made less threatening, thanks to a new therapy reported in the 1 August issue of Blood. The treatment--so far only examined in test tubes--targets a gene mutation specific to the cancer cells, leaving healthy cells unharmed.

In acute myeloid leukemia, undifferentiated bone marrow cells grow uncontrollably in the blood and bone marrow, crowding out and destroying healthy cells. The condition usually results from multiple changes to the DNA. One such mutation, found in about 25% of acute leukemia patients, involves a gene known as FLT3, which encodes an enzyme called a kinase that usually promotes cell division in a controlled way. Like a brick on the gas pedal, the mutated FLT3 stimulates cell division ceaselessly. Current chemotherapy treatments cure the disease in fewer than 10% of patients who have a FLT3 mutation--partly because toxic chemotherapy drugs can be used for only a few days at a time, not killing as many cancer cells as they might.

A research team led by oncologist Donald Small at Johns Hopkins University in Baltimore decided to see if a drug that targets FLT3 would have fewer side effects. They treated a variety of healthy tissues and 23 samples of cancer cells taken from leukemia patients with AG1295, a drug known to selectively block the kinase. Of the 23 samples, eight had FLT3 mutations. Comparing the drug with a known chemotherapy agent, the team found that after 72 hours, AG1295 had killed nearly half the cancer cells that contained a FLT3 mutation and none of the cells that did not, while the chemotherapy agent killed cells with or without FLT3 mutations with equal vigor. AG1295 won't work inside the body because it can't get to the marrow, but Small says his team has already identified other FLT3 inhibitors potentially useful for patients, and clinical trials are just around the corner.

Leukemia researcher Brian Druker of Oregon Health and Science University praises the work, calling FLT3 "one of the best targets in all of acute leukemia, because it's one of the most common." Combined with chemotherapy, Druker says, "this will lead to better treatments for acute leukemia."

Related sites

Abstract of the research paper
Donald Small's page at Johns Hopkins University
Brian Druker's page at Oregon Health and Science University
Adult Acute Myeloid Leukemia, from the National Cancer Institute's CancerNet