Direct targeted therapy for MLL-fusion-driven high-risk acute leukaemias.

ABSTRACT:

Background

Improving the poor prognosis of infant leukaemias remains an unmet clinical need. This disease is a prototypical fusion oncoprotein-driven paediatric cancer, with MLL (KMT2A)-fusions present in most cases. Direct targeting of these driving oncoproteins represents a unique therapeutic opportunity. This rationale led us to initiate a drug screening with the aim of discovering drugs that can block MLL-fusion oncoproteins.

Methods

A screen for inhibition of MLL-fusion proteins was developed that overcomes the traditional limitations of targeting transcription factors. This luciferase reporter-based screen, together with a secondary western blot screen, was used to prioritize compounds. We characterized the lead compound, disulfiram (DSF), based on its efficient ablati

SUBMITTER: Cantilena S 

PROVIDER: S-EPMC9214753 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature