Blocking enzyme may help childhood leukemia: study

By Julie Steenhuysen

CHICAGO (Reuters) - A simple enzyme may hold the key to tackling a hard-to-treat type of leukemia in babies, U.S. researchers said on Monday.

The finding could also form the basis for a new class of cancer drugs, the researchers said.

They said blocking the enzyme may keep an abnormal protein called Dot1 from flipping on genetic switches that cause a deadly form of acute lymphoblastic leukemia or ALL.

"The way that this protein causes harm is by recruiting this enzyme and turning on genes that shouldn't be turned on," said Dr. Scott Armstrong of Children's Hospital Boston, whose research appears in the journal Cancer Cell.

"If you turn the enzyme off, which we've done, the genes that shouldn't be on are turned off," Armstrong said in a telephone interview.

Armstrong said the finding could lead to a much-needed new therapy for children with this type of ALL and it may hold promise for other cancers as well.

"There are a bunch of different enzymes like Dot1 that are implicated in different types of cancers," Armstrong said. "Inhibiting enzymes like Dot1 might be a therapy opportunity in many different cancers."

Armstrong and colleagues conducted a series of studies on mice with this form of ALL.

They found that the abnormal protein -- called MML-AF4 -- needs the help of the enzyme Dot1 to make changes in the cell. It uses Dot1 to alter another type of a protein called a histone that turns on the cancer switches.

When they used a genetic engineering technique to switch off Dot1, the genes that were switched on reverted to their original state.

A study of cell samples from children with this type of leukemia suggest the same process is going on in humans.

Armstrong said the need for better treatments is especially dire in this form of ALL, which makes up about 5 percent of total ALL cases, but 70 percent of cases in infants.

"We cure about 80 percent of children with ALL, but if kids have ALL with this gene abnormality, we cure them less than 50 percent of the time," Armstrong said.

Armstrong said drugmakers are already working on drugs to block similar types of enzymes, such as histone deacetylases inhibitors or HDACs.

One, Merck & Co Inc's Zolinza, is already approved in the United States to treat cutaneous T cell lymphoma, a type of skin cancer.