Nav: Home

Epigenetic protein could be new therapeutic target in acute myeloid leukemia

March 19, 2019

British researchers have discovered that an epigenetic protein called EZH2 delays the development of acute myeloid leukemia (AML) but then switches sides once the disease is established to help maintain tumor growth. The study, which will be published March 19 in the Journal of Experimental Medicine, suggests that targeting EZH2 could therefore be an effective treatment for AML, an aggressive blood cancer expected to kill over 10,000 people in the US alone this year.

EZH2 is an epigenetic protein that can control the activity of hundreds of genes by chemically modifying the histone proteins that package up the cell's DNA. Increases in EZH2 activity are thought to promote the development of a variety of human tumors, including breast and prostate cancers, and several clinical trials are currently investigating whether drugs that prevent EZH2 from modifying histones could be used as cancer treatments.

Whether EZH2 also promotes the development of blood cancers like AML is unclear, however. Some evidence suggests that the epigenetic protein many actually prevent AML and other myeloid malignancies.

A team of researchers led by Professor Brian Huntly at the Cambridge Institute for Medical Research, UK, found that mice lacking EZH2 developed AML much faster than usual, indicating that the protein does indeed delay the development of AML. However, once AML had fully developed and established itself in the mice, deleting the EZH2 gene or inhibiting the EZH2 protein with a drug disrupted tumor growth and significantly prolonged the animals' survival. Inhibiting EZH2 also prevented the growth of AML cells isolated from patients.

Huntly and colleagues found that inhibiting EZH2 has conflicting effects on the development and maintenance of AML because the protein regulates almost completely different sets of genes at early and late stages of the disease. For example, during the initial stages of AML, loss of EZH2 causes cells to increase production of a transcription factor called Plag1 that accelerates the development of leukemia. But inhibiting EZH2 at later stages of AML has no effect on Plag1 levels.

"Our findings uncover novel and dramatically opposing functions of EZH2 during AML that appear dependent upon the phase of disease, with EZH2 functioning as a tumor suppressor in AML induction and as a facilitator of disease in established AML," Huntly says. "To our knowledge, this is the first description of an epigenetic regulator having both tumor-suppressive and oncogenic function in different phases of the same cancer. In addition, our work validates EZH2 as a therapeutic target with the potential to treat several different subtypes of AML."



Basheer et al. 2019. J. Exp. Med.http://jem.rupress.org/cgi/doi/10.1084/jem.20181276?PR
-end-
About the Journal of Experimental Medicine

The Journal of Experimental Medicine (JEM) features peer-reviewed research on immunology, cancer biology, stem cell biology, microbial pathogenesis, vascular biology, and neurobiology. All editorial decisions are made by research-active scientists in conjunction with in-house scientific editors. JEM makes all of its content free online no later than six months after publication. Established in 1896, JEM is published by Rockefeller University Press. For more information, visit jem.org.

Visit our Newsroom, and sign up for a weekly preview of articles to be published. Embargoed media alerts are for journalists only.

Follow JEM on Twitter at @JExpMed and @RockUPress.

Rockefeller University Press

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Anthropomorphic
Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...