Identification of specific drug sensitivities to eradicate leukemic stem cells

Acute Myeloid Leukemia (AML) is a form of blood cancer that is still difficult to cure. The average 5-year survival rate is currently less than 30%. AML is particularly prevalent in older patients over the age of 65. As our society continues to age, this will increasingly place a greater social and economic burden on our society in the coming decades. Better treatment methods are clearly needed. Within this project proposal, we focus on small molecules that can target the epigenome. It has become clear in recent years that mutations often occur in enzymes that control the epigenome, resulting in significant changes to the epigenome in AML patients. On the other hand, work by us and others has also shown that AML is a highly heterogeneous disease, with the combination of mutations causing leukemia varying greatly from patient to patient. Therefore, a patient-specific approach is also necessary. 

Janssen has identified promising drug candidates (targets) that could lead to better treatment for AML patients. As a continuation of a long-standing collaboration between the Schuringa lab (UMCG) and Janssen, we now want to study these new promising targets in detail. Additionally, we will conduct a quantitative proteome screen to link drug sensitivity to specific DNA mutations and signal transduction networks. Ultimately, our studies could lead to the development of more effective and patient-specific treatment methods for AML patients. Some of the results are currently under review by a peer-reviewed journal.