Researchers identify new strategy for interfering with potent cancer-causing gene

February 11, 2013, Cold Spring Harbor Laboratory

Acute myeloid leukemia (AML) is an aggressive blood cancer that is currently incurable in 70% of patients. In a bold effort, CSHL scientists are among those identifying and characterizing the molecular mechanisms responsible for this cancer in order to generate potential new therapeutics.

CSHL Assistant Professor Christopher Vakoc, M.D., Ph.D., and colleagues, including the group of Professor Robert Roeder Ph.D. at The Rockefeller University, report the characterization of a protein required for AML in a paper published today in the Proceedings of the National Academy of Sciences.

Screening of DNA packaging proteins calls attention to RNF20

About 5%-10% of AML is characterized by the rearrangement of a gene called MLL (Mixed-Lineage Leukemia). The MLL that result from this rearrangement are potent oncogenes—cancer-causing genes. They are particularly common in infant acute leukemia, which is usually resistant to standard chemotherapy.

An emerging body of evidence implicates problems with chromatin, the packaging material for DNA within the , as a major cause of . Based on this, Vakoc's laboratory is searching for targets among chromatin proteins, with the hope of identifying new ways to fight this disease.

"We sifted through a class of proteins that add 'protein tags' to chromatin in a search for new therapeutic targets", says Eric Wang, a former technician in the Vakoc lab who led this study. Wang is currently a doctoral student at Johns Hopkins University. These 'protein tags' are called ubiquitin and constitute one of many ways to control which genes are switched 'ON' or 'OFF' in our cells.

The team identified a protein called RNF20 that attaches ubiquitin tags to chromatin as being essential for the formation of leukemias caused by MLL-rearrangements. When they suppressed the expression of RNF20, the researchers were able to decrease proliferation in living mice, extending their lifespan.

Upon closer examination, the team realized that by targeting RNF20 they prevent MLL-fusion proteins from being able to work. "When we reduce the levels of RNF20 in leukemia cells, they revert back to being more like normal blood cells", says Shinpei Kawaoka, a postdoc in the Vakoc lab who also was involved in the study.

Vakoc's team proposes a model in which leukemia cells of the MLL-rearranged subtype come to rely on RNF20 to maintain their gene expression program, implicating it as a potential therapeutic target. Small-molecule drugs that target other proteins involved in regulating ubiquitin tags already exist so it is possible that drugs targeting RNF20 could be developed in the future for the treatment of MLL-rearranged leukemia.

Explore further: Possible new approach to treating deadly leukemia in babies

More information: "Histone H2B ubiquitin ligase RNF20 is required for MLL-rearranged leukemia" is published online in the Proceedings of the National Academy of Sciences on February 11, 2013. The authors are: Eric Wang, Shinpei Kawaoka, Ming Yu, Junwei Shi, Ting Ni, Wenjing Yang, Jun Zhu, Robert G. Roeder and Christopher R. Vakoc. doi: 10.1073/pnas.201301045

Related Stories

Possible new approach to treating deadly leukemia in babies

April 13, 2011
A Loyola University Health System study points to a promising new approach to treating an aggressive and usually fatal leukemia in babies.

'Druggable' protein complex identified as a therapeutic target in acute myeloid leukemia

April 2, 2012
Scientists at Cold Spring Harbor Laboratory have identified a candidate drug target for treating acute myeloid leukemia (AML), a white blood cell cancer that proliferates out of control in the bone marrow. The team, led by ...

Recommended for you

Researchers create a drug to extend the lives of men with prostate cancer

March 16, 2018
Fifteen years ago, Michael Jung was already an eminent scientist when his wife asked him a question that would change his career, and extend the lives of many men with a particularly lethal form of prostate cancer.

Machine-learning algorithm used to identify specific types of brain tumors

March 15, 2018
An international team of researchers has used methylation fingerprinting data as input to a machine-learning algorithm to identify different types of brain tumors. In their paper published in the journal Nature, the team ...

Higher doses of radiation don't improve survival in prostate cancer

March 15, 2018
A new study shows that higher doses of radiation do not improve survival for many patients with prostate cancer, compared with the standard radiation treatment. The analysis, which included 104 radiation therapy oncology ...

Joint supplement speeds melanoma cell growth

March 15, 2018
Chondroitin sulfate, a dietary supplement taken to strengthen joints, can speed the growth of a type of melanoma, according to experiments conducted in cell culture and mouse models.

Improved capture of cancer cells in blood could help track disease

March 15, 2018
Tumor cells circulating throughout the body in blood vessels have long been feared as harbingers of metastasizing cancer - even though most free-floating cancer cells will not go on to establish a new tumor.

Area surrounding a tumor impacts how breast cancer cells grow

March 14, 2018
Cancer is typically thought of as a tumor that needs to be removed or an area that needs to be treated with radiation or chemotherapy. As a physicist and cancer researcher, Joe Gray, Ph.D., thinks differently.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.