BioCentury
ARTICLE | Preclinical News

FLT3 degradation via USP10 could treat AML

October 5, 2017 6:53 PM UTC

In a paper published in Nature Chemical Biology, researchers at Dana-Farber Cancer Institute and colleagues identified ubiquitin specific peptidase 10 (USP10), a deubiquitinating enzyme (DUB), as a target to degrade FMS-like tyrosine kinase 3 (FLT3; CD135), suggesting a new strategy to treat acute myelogenous leukemia.

Using a whole-cell phenotypic screen of DUB inhibitors, researchers identified two small molecule USP10 inhibitors that selectively killed cells expressing FLT3-internal tandem duplication (ITD) mutations found in AML. In mice, the compounds abolished AML-induced FLT3 expression and reduced leukemia burden compared to vehicle controls...