Scientists identify novel enzyme with key role in leukemia protein's normal function

October 31, 2003

BOSTON-Dana-Farber Cancer Institute scientists have discovered an enzyme they say accounts for a cancer-causing protein's Jekyll-and-Hyde personality. Normally, the protein regulates when and how body parts develop, but when mutated, it triggers a rare, often-lethal infant leukemia called mixed lineage leukemia.

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.

The Dana-Farber scientists say that enzymes such as Taspase1 can make good targets for cancer drugs and they can be inhibited with oral, relatively non-toxic compounds. Thus, a drug that blocks Taspase1 might shut down the runaway proliferation of blood cells that causes the leukemia - and might work in other cancers as well.

"We'd be very interested in making an inhibitor to Taspase1, which could knock the HOX genes out of action, and test whether cancers are addicted to their HOX genes," said Korsmeyer, who is the Sidney Farber Professor of Pathology at Harvard Medical School and a Howard Hughes Medical Institute investigator.

Gary Gilliland, MD, PhD, a leukemia specialist at Dana-Farber and Brigham and Women's Hospital, commented on the paper in an accompanying editorial. Further research to follow up this new lead, he wrote, "should provide further insight into the potential therapeutic value of Taspase inhibitors in treatment of leukemia associated with MLL gene rearrangements." The research was supported in part by grants from the National Institutes of Health.
-end-
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Dana-Farber Cancer Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.