Researchers in the United States and the United Kingdom believe they have found a new gene target that could aid in the development of more effective treatments for acute myeloid leukemia (AML).
Inhibition of the METTL3 gene allowed for the destruction of AML in human and mouse cells without damaging healthy blood cells, the researchers reported in a research letter published Nov. 27 in the journal Nature.
“This study uncovered an entirely new mechanism of gene regulation in AML that operates through modifications of RNA,” study author Konstantinos Tzelepis of the Wellcome Trust Sanger Institute, Cambridge (England), said in a statement . “We discovered that inhibiting the methyl transferase activity of METTL3 would stop the translation of a whole set of proteins that the leukemia needs. This mechanism shows that a drug to inhibit methylation could be effective against AML without affecting normal cells.”
Using mouse cells, the researchers used CRISPR-Cas9 gene editing technology to identify RNA-modifying enzymes that are needed for the survival and proliferation of AML cells. They identified 46 potential candidate genes and further narrowed that to the METTL gene families. They next targeted METTL1, METTL3, METTL14, and METTL16 in 10 human AML cell lines and 10 cell lines from heterogeneous cancer types. METTL3 was shown to have the strongest effect.
Read the full research letter in Nature ( doi: 10.1038/nature24678 ).
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