Cell Sub-Journal: CRISPR screening tool to identify new drug targets for leukemia

According to a new study published by Penn Medicine on the Molecular Cell website, the CRISPR screening tool has identified a new therapeutic target for the treatment of acute myeloid leukemia (AML).

"We found that cancer cell AML patients rely heavily on ZMYND8, and because of the complex CRISPR-based screening method, we found the exact "pharmaceutical pocket" target," said Junwei senior author Shi, Ph.

Cao Zhendong, a doctoral student in Shi's laboratory, added: “These findings indicate that giving ZMYND8 drug inhibitors can disrupt the fragile gene regulatory circuit of AML

Acute myeloid leukemia affects more than 20,000 patients each year, including children and adults, and the 5-year survival rate for patients over 20 years old is only 27%

CRISPR not only enables scientists to modify genes more easily and at a lower cost than previous methods, but also enables them to simultaneously screen thousands of specific functional protein domains with therapeutic targeting potential

Researchers use CRISPR to precisely destroy the domain functions of proteins in cancer cells, map their molecular functions, and modify them for use in mouse models

The researchers also discovered a biomarker—the expression level or epigenetic status of the IRF8 gene in AML cells—to predict the sensitivity of cancer cells to ZMYND8 inhibitors

"Many genetic and epigenetic changes have been found in cancer, but there are very few actionable targets," said co-author Dr.

This research was supported by the Linda Pechenik Montague Investigator Award, research sponsored by Cold Spring Harbor Laboratory, and a startup package from the University of Pennsylvania