Impact of the Tumor ECM Niche On AML Drug Sensitivity: A Comparative Screening Study

Abstract

Acute myeloid leukemia (AML) progression and drug resistance are strongly shaped by interactions between leukemic cells and the extracellular matrix (ECM) within the bone marrow niche. These ECM-driven signals promote cell survival and reduce therapeutic sensitivity, contributing to treatment failure and relapse. Traditional two-dimensional polystyrene cultures do not recapitulate these microenvironmental cues, limiting their predictive value for preclinical drug screening. Scaffold-based culture systems offer a more physiologically relevant model by mimicking ECM architecture and enabling cell–matrix interactions. However, quantifying drug responses in these complex systems is challenging, as conventional assays including plate-based viability, flow cytometry and high-content imaging, have distinct limitations.

In this study, we optimized and compared these methods to evaluate AML drug responses in both polystyrene and ECM-mimicking scaffolds. Flow cytometry enabled reliable assessment of cell viability and revealed clear differences in drug sensitivity between the two platforms. This comparative approach highlights the impact of the ECM microenvironment on therapeutic responses, improving the evaluation of candidate AML drugs.