Laminin Receptor Characterization in Acute Myeloid Leukemia: Integrin α7β1 Defines non-Leukemic Stem Cells with Migratory Potential

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 receptor expression with stemness in healthy hematopoiesis, the role of laminin receptors 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 mRNA expression of all four laminin receptors correlates with poor overall survival. Notably, integrin α6 and α7 display the highest cell surface presentation among the examined laminin receptors and are higher expressed on AML cells compared to healthy controls. Moreover, our results indicate that integrin α7 expression allows to distinguish between leukemic stem cells (LSC) and non-LSC populations. Specifically, integrin α7 appears to mark non-LSC with enhanced migratory potential. Together, our results confirm the association of high laminin receptor expression with poor prognosis and establish integrin α7 as marker of high migratory non-LSC. ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. * A : ampere ACK : ammonium–chloride–potassium AML : acute myeloid leukemia BCAM : basal cell adhesion molecule BM : bone marrow BSA : bovine serum albumin Cas9 : CRISPR associated protein 9 CB : cord blood cDNA : complementary DNA CFU : colony-forming unit cm2 : square centimeters DAPI : 4′,6-diamidin-2-phenylindol ddH2O : double-distilled water DEG : differentially expressed genes DMSO : dimethyl sulfoxide ECM : extracellular matrix EDTA : ethylene diamine tetraacetic acid ELN : European leukemiaNet EMT : epithelial-to mesenchymal transition FACS : fluorescence-activated cell sorting FBS : fetal bovine serum FC : fold change FDR : false discovery rate FLT3-L : fms-related receptor tyrosine kinase 3 ligand g : gram GAPDH : glyceraldehyde 3-phosphate dehydrogenase Gb : giga base G-CSF : granulocyte colony-stimulating factor GTEx : genotype-tissue expression GSEA : gene set enrichment analysis h : hours HKG : housekeeping gene HSPC : hematopoietic stem and progenitor cell HUVEC : human umbilical vein endothelial cells IL-3 : interleukin-3 IL-6 : interleukin-6 ITGA3 : gene encoding integrin α3 ITGA6 : gene encoding integrin α6 ITGA7 : gene encoding integrin α7 KO : knockout l : liter LM : laminin LSC : leukemic stem cell µg : microgram µL : microliter mg : milligram min : minutes mL : milliliter mM : millimolar MNC : mononuclear cell NFκB : nuclear factor kappa-light-chain-enhancer of activated B cells NKG2DL : natural killer group 2D ligand nm : nanometer nmol : nanomol OD : optical density PB : peripheral blood PBMC : peripheral blood mononuclear cells PBS : phosphate-buffered saline PCR : polymerase chain reaction Pmol : picomol qRT-PCR : quantitative real-time polymerase chain reaction RNP : ribonucleoprotein RT : room temperature SCF : stem cell factor SDC2 : syndecan-2 SDS : sodium dodecyl sulfate SDS-PAGE : sodium dodecyl sulfate polyacrylamide gel electrophoresis sgRNA : single guide RNA SR-1 : StemRegenin 1 TBP : TATA-binding protein TBST : Tris-buffered saline with Tween20 TCGA : the cancer genome atlas THBS1 : thrombospondin 1 TNFα : tumor necrosis factor alpha tpm : transcripts per million TPO : thrombopoietin UM729 : pyrimido-indole derivate V : volt VCAN : versican [1]: pending:yes