Drug Repositioning in Infant Leukaemia

Introduction:

Despite an overall improvement in the prognosis of childhood leukaemia, survival rates for infants still remain poor. Many of these leukaemias are driven by mixed lineage leukaemia (MLL) gene rearrangements. Therefore, a therapy that could degrade MLL-rearranged genes could be a potential treatment. Drug repositioning, identifying a novel clinical use for an already approved drug, is a more beneficial route than typical drug discovery as it uses de-risked compounds developed with lower costs over a shorter time. Previously the lab carried out a drug screen to identify clinically approved drugs that could degrade MLL fusion proteins. The purpose of this study was to validate and characterise one of these positive hits.

Methods:

Western blot was used to measure MLL fusion protein degradation and qPCR was used to measure gene expression. TOPRO assays were used to measure cell death.

Results:

We showed in a panel of human MLL-rearranged leukaemic cell lines that drug treatment reduced expression of MLL fusion protein and its target genes and affects cell death.

Conclusion:

We have validated this drug as a positive hit and continue to characterise its action.