Research in AML

A series of Acute myeloid leukemia (AML) targets identified either in the ongoing research activities within JJ Schuringa’s lab (continuation of the previous research activities within J&J contract) or proposed by Janssen were selected for further detailed analyses in vitro and in vivo.

Impact:

AML is a form of blood cancer whereby the immature hematopoietic stem/progenitor cells fail to differentiate towards fully functional mature blood cells. Unfortunately, AML is still difficult to cure. Survival rates heavily depend on the AML subtype but on average have remained less than 30%. Clearly, better treatment options are needed to improve the outcomes of this dismal disease.

Approach:

In vitro characterisation of selected targets will include inhibitor studies and functional knock-down or knock-out studies to evaluate effects on cell cycle progression, long-term self-renewal, apoptosis, differentiation, and stem cell quiescence. The downstream pathways of the candidate target will be investigated using multiomics approaches, including genetics and quantitative proteomics.

The aim is to identify AML-subtype-specific drug vulnerabilities. Our combinatorial approach will uncover the genetic and signaling networks that underlie rug sensitivities. Ultimately, these results should allow the development of more effective treatment modalities for AML patients.