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Protein 'reader' ENL tied to common leukemia

Discovery suggests potential for BET inhibitor drugs as treatment for acute myeloid leukemia

Date:
March 1, 2017
Source:
University of Texas M. D. Anderson Cancer Center
Summary:
Anyone who uses an employee badge to enter a building may understand how a protein called ENL opens new possibilities for treating acute myeloid leukemia (AML), a fast-growing cancer of bone marrow and blood cells and the second most common type of leukemia in children and adults.
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Anyone who uses an employee badge to enter a building may understand how a protein called ENL opens new possibilities for treating acute myeloid leukemia (AML), a fast-growing cancer of bone marrow and blood cells and the second most common type of leukemia in children and adults.

Findings from a study at The University of Texas MD Anderson Cancer Center revealed the leukemia-boosting abilities of ENL, which contains a protein component called YEATS that "reads" histone proteins. Histone proteins make up chromatin, large clusters of DNA- and RNA-containing molecules comprising our body's chromosomes. Just as a scanner "reads" data on an identification badge, ENL recognizes a type of histone modification known as acetylation.

Research results, which build upon a previous MD Anderson study of histone-reading proteins, are published in the March 1 online issue of Nature. The findings indicated treatment against ENL with a class of experimental drugs called bromodomain and extra-terminal (BET) inhibitors may be effective for treating AML.

"Our study showed that ENL is required for disease maintenance in AML," said Xiaobing Shi, Ph.D., associate professor of Epigenetics and Molecular Carcinogenesis. "Depletion of ENL led to anti-leukemic effects, suppressing growth both in vivo and in vitro. Notably, disrupting ENL further sensitized leukemia cells to BET inhibitors."

Histone modifications like acetylation serve as docking sites for reader proteins which recognize specific modifications, influencing downstream biological outcomes. While many such reader proteins have been identified for histone modifications called methylation, few are known to recognize histone acetylation.

Shi's team employed CRISPR, a gene-editing tool, to deplete ENL and suppress cancer gene expression, which was crucial given that cancer cells often co-opt chromatin regulatory pathways.

"Targeting epigenetic readers represents a class of anti-cancer therapy that we believe holds clinical promise," said Hong Wen, Ph.D., research assistant professor of Epigenetics and Molecular Carcinogenesis and co-first author of the paper. "Our study revealed ENL as a chromatin reader that regulates oncogenic programs, thus establishing ENL as a potential drug target for AML."


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Materials provided by University of Texas M. D. Anderson Cancer Center. Note: Content may be edited for style and length.


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University of Texas M. D. Anderson Cancer Center. "Protein 'reader' ENL tied to common leukemia: Discovery suggests potential for BET inhibitor drugs as treatment for acute myeloid leukemia." ScienceDaily. ScienceDaily, 1 March 2017. <www.sciencedaily.com/releases/2017/03/170301132009.htm>.
University of Texas M. D. Anderson Cancer Center. (2017, March 1). Protein 'reader' ENL tied to common leukemia: Discovery suggests potential for BET inhibitor drugs as treatment for acute myeloid leukemia. ScienceDaily. Retrieved March 27, 2017 from www.sciencedaily.com/releases/2017/03/170301132009.htm
University of Texas M. D. Anderson Cancer Center. "Protein 'reader' ENL tied to common leukemia: Discovery suggests potential for BET inhibitor drugs as treatment for acute myeloid leukemia." ScienceDaily. www.sciencedaily.com/releases/2017/03/170301132009.htm (accessed March 27, 2017).