myeloid leukemia (AML) is a fast-growing cancer of bone marrow and blood
cells and the second most common type of leukemia in children and
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.
‘Depletion of ENL led to anti-leukemic effects, suppressing growth both in vivo and in vitro.’
Research results, which build upon a previous MD Anderson study of
histone-reading proteins, are published in the 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, 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, 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."