The newly identified protease enzyme, Taspase1, plays a key role in the MLL protein's dual-personality. (A protease enzyme cuts protein molecules into smaller pieces). Blocking Taspase1, the researchers say, might provide a novel way to shut down runaway production of cancer cells. The findings are reported in the Oct. 31 issue of Cell.
"These findings demonstrate that a simple protease enzyme is required for the effects of this gene (MLL) and suggests that protease inhibitors, which have been effective with relatively few side effects in other diseases, could be a reasonable way to treat cancer," says Stanley Korsmeyer, MD, senior author of the paper.
Mixed lineage leukemia strikes fewer than 100 babies every year in the United States, but it is typically fatal in 60 percent. It is caused by damage to the MLL gene, which then makes a mutant MLL protein.
James Hsieh, MD, PhD, and Emily Cheng, PhD, are the paper's first and second authors, respectively. Both are members of Korsmeyer's laboratory.
Hsieh, Cheng and their colleagues found that in its normal state, the MLL protein switches on and regulates a special set of genes known as HOX genes. This gene set is the master controller of the development of the body in embryonic life according to a predetermined plan. The researchers now have shown that MLL cannot switch on the HOX genes without the newly discovered Taspase1 enzyme, whose task is to cut the full MLL protein into two smaller, active pieces. If HOX genes are revved up too high, blood cells are overproduced, and the patient develops leukemia.