Intrinsic and acquired resistances are the main reason for failure of current treatments of blood cancer patients not eligible for curative transplantation. Acute myeloid leukemia (AML) is among the most devastating cancers worldwide with overall 5-year survival rates of less than 30%. The goal of our study will be to identify new combinatorial therapies in AML. Specifically, we propose the following objectives:

– To perform a genetic screen identifying sensitizers to chemotherapy in AML. We will perform a knockout screen in the presence and absence of chemotherapy in two AML cell lines.

– To validate top hits with available drugs and tool compounds. We will validate selected hits using semi-automated imaging approaches. We will analyze the best validated combinations in an extended cell line panel as well as in primary AML cells.

– To understand the mode of action. We will dissect the underlying mechanism of action of the most promising drug combinations.

– To test most promising combinations in preclinical in vivo AML models. In parallel to objective 3, the most promising drug combination will be examined in vivo AML models.

If you want to know more, please contact Jeannine Diesch or Marcus Buschbeck at jdiesch@carrerasresearch.org and mbuschbeck@carrerasresearch.org.

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