Elucidating Leukemic Stem Cell Interactions with the Tumor Extra Cellular Matrix Niche

Abstract

Stem cells in niches rely on the extracellular matrix (ECM) for structural support and behavioral regulation. ECM composition is critical for tissue health; alterations can lead to diseases like acute myeloid leukemia (AML). Studies show myeloid malignancies alter hematopoietic niches to support leukemic growth, underscoring the importance of cell-ECM interactions. Our study aimed to identify effective ECM combinations for culturing primary AML samples. We tested patient-derived mononuclear cells on 18 ECM-enriched matrices, including collagen, elastin, and hydroxyapatite. Post a 72-hour incubation, we evaluated cell viability and progenitor potential using colony-forming unit assays, finding conditions that enhance cell life and maintain stem cell potential. Additionally, we identified key ECM genes overexpressed in leukemic versus normal cells and conducted in silico screening of a 1280 compound drug library, targeting αM/β2 integrin. These insights enable future ex vivo AML studies and shed light on niche mechanisms in health and disease.