MAR 11, 2017 12:30 PM PST

A new way to Alter Gene Expression may aid Leukemia Treatment

WRITTEN BY: Carmen Leitch

New work by scientists at Rockefeller University in New York could help young patients suffering from leukemia. They engineered a new method to reprogram gene expression in cells; it has the potential to be used in combination therapies against a cancer that is known for genomic instability and drug resistance. The video below summarizes the work, which was reported in Nature.

Leukemia refers to a class of cancers that affect the bone marrow and blood or lymphatic tissue; there are many types affecting a wide range of people. While there are many kinds of treatment as well, depending on the diagnosis and the individual, those treatments are not always effective. Scientists are exploring a treatment avenue that targets proteins of the cell called histones in various ways. 

Histones have an important role in the organization of DNA and can thus exert an effect on the expression of genes that in turn regulate cellular functions that influence tumor growth. The cell has special proteins that act as readers, interpreting chemical tags on histones that act to turn gene expression on or off. One type of reader protein, BET, has been targeted in cancer therapeutics; inhibition of BET proteins is one kind of cancer therapy.

In this work, the researchers have found another class of reader proteins that can be manipulated in cancer therapeutics just as BET proteins have been. A protein feature, a functional domain called YEATS, identifies acetyl groups tagging histones and has been correlated to a poor prognosis in patients.

"The functional importance of this reading activity by the YEATS domain was unknown," explained Liling Wan, a researcher in the Laboratory of Chromatin Biology and Epigenetics at Rockefeller University.

In many leukemia patients, blood cells carry a gene fusion that can lead to cancer-activating changes in gene expression. / Credit: Rockefeller University

One genomic instability in leukemia patients is a rearrangement of the genome that fuses a gene encosing for the MLL protein, with proteins containing YEATS domains. One such protein is ENL. Young patients carrying leukemia with these features do not fare well. "In infants, it occurs in more than 70 percent of acute lymphoid leukemia and in more than 35 percent of acute myeloid leukemia cases," said Wan.

This work has demonstrated that ENL could be promoting the growth of tumors and as such, makes for a good drug target to inhibit the process. 

The researchers used CRISPR/Cas9 technology to investigate the influence of ENL on leukemia. In mice that carried leukemia cells that were depleted of ENL there were better outcomes compared with mice that carried typical leukemia cells. Leukemia engineered to lack ENL did not proliferate as rapidly and the mice transplanted with those cells lived longer.

"We look forward to the development of new drugs that can block YEATS domain function, perhaps working in concert with existing bromodomain inhibitors that are already in clinical trials," comented David Allis, head of the Laboratory of Chromatin Biology and Epigenetics.

Sources: UPI via The Rockefeller University, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
AUG 14, 2018
Cancer
AUG 14, 2018
Can Zika Virus Help Neuroblastoma Patients?
Researchers in Florida published the potential for Zika virus to help in the treatment of Neuroblastoma in patients of all ages....
OCT 06, 2018
Genetics & Genomics
OCT 06, 2018
Genetic Mutation Linked to Increased Pancreatic Cancer Risk in Women
In a first, researchers have found a genetic mutation that has a sex-specific effect on pancreatic cancer risk....
OCT 25, 2018
Health & Medicine
OCT 25, 2018
Sedentary Lifestyle More Deadly Than Smoking
A number of recent studies have found that first cardiovascular associations with regular high-intensity exercise. These studies......
NOV 05, 2018
Videos
NOV 05, 2018
How UV Rays Cause Aging and Skin Cancer
We know that UV rays can do damage to our DNA - but how?...
NOV 22, 2018
Cell & Molecular Biology
NOV 22, 2018
Stopping Cancer Cells in Their Tracks
Researchers at the University of Minnesota have developed a technique to stop the movement of cancer cells....
DEC 04, 2018
Drug Discovery
DEC 04, 2018
Drug Combination May Be Effective for Melanoma
Protein kinase inhibitors have been noted to be the most effective class of drugs in the treatment of melanoma—a deadly skin cancer of the melanocyte...
Loading Comments...