Laminin receptor characterization in acute myeloid leukemia: integrin α7β1 defines leukemic cells with migratory potential

Abstract

Interactions with the bone marrow (BM) niche are crucial for promoting self-renewal and survival of acute myeloid leukemia (AML) cells. Consequently, AML cells express a variety of surface receptors to engage with BM niche cells and extracellular matrix proteins, including laminins. Despite the association of laminin receptors with stemness in healthy hematopoiesis, their role in AML remains poorly understood. In this study, we present a comprehensive examination of the laminin receptors integrin α3β1, α6β1, α7β1, and basal cell adhesion molecule (BCAM) in AML. We demonstrate that high messenger RNA (mRNA) expression of all four laminin receptors correlates with poor overall survival. Notably, integrin α6 (ITGA6) and integrin α7 (ITGA7) display the highest cell surface density among the examined laminin receptors and are more highly expressed on AML cells compared with healthy controls. Moreover, our results indicate that the absence of ITGA7 expression can identify cells with increased colony-forming potential, even in patients who are negative for the stem cell marker CD34, usually used to enrich leukemic stem cells (LSCs). Reanalyzing survival data from The Cancer Genome Atlas (TCGA)-AML cohort, ITGA7 expression further allows refinement of the risk stratification based on the LSC score, where low LSC and ITGA7 levels confer superior survival. Lastly, ITGA7 appears to mark leukemic cells with enhanced migratory potential, which can be inhibited by the anti-ITGA7 blocking antibody in vitro and in vivo. Together, our results confirm the association of high laminin receptor expression with poor prognosis and ITGA7 as a marker of high migratory leukemic cells.