Architecture and Trajectory of Acquired Resistance to Therapy in AML

The Program's long-term goal is to uncover mechanisms of acquired drug resistance in acute myeloid leukemia (AML) to develop new drug combinations that prevent relapse and improve patient outcomes. Despite recent advancements, the five-year survival rate for AML remains at 20%, unchanged for decades. Though seven new AML therapies have been approved, they have not led to lasting results, as relapse is driven by complex interactions between tumor cells and the bone marrow microenvironment.

The ARTNet AML Center brings together investigators who have collaborated for over 15 years, including within the DRSN consortium, ARTNet's predecessor. Their past work includes creating the largest functional genomic dataset on AML, conducting genome-wide CRISPR screens, studying AML’s interactions with stromal and immune cells, and testing various drug combinations. This research has resulted in over 150 publications, continuous funding, extensive datasets in public repositories, and several clinical trials.

The Center's hypothesis is that acquired drug resistance is influenced by both external and internal factors over time. Understanding this trajectory could help identify timely therapeutic strategies to prevent resistance and stay ahead of tumor evolution. Three integrated projects will explore: 1) how AML cells adapt to evade therapy using CRISPR screens and primary patient samples, 2) how the stromal and immune microenvironment influences resistance using co-culture models and computational strategies, and 3) how resistance signatures and drug combinations can be translated into clinical practice using advanced bone marrow models and patient specimens.

There are 3 projects in AML center:

The Center will be supported by an Administrative Core and a Functional Phenotyping Core, aiming to develop a deep understanding of AML resistance and identify new treatment regimens to prevent relapse and achieve lasting remissions.

The Principal Investigators of AML center are Drs. Jeff Tyner, Shannon McWeeney and Brian Druker