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. 2022 Jan 18;9:798604. doi: 10.3389/fcell.2021.798604

FIGURE 1.

FIGURE 1

Cell-cell interactions within the BM microenvironment are shaped by adhesion and metabolism. (A) HSC/HSPC/LSC express adhesion receptors such as α4β1, CD44, and CXCR4. These receptors interact with their specific ligands such as VCAM-1, HA, and CXCL12 on non-hematopoietic cells such as stromal cells, MSCs and osteoblasts and contribute HSC quiescence. (B) The vascular niche made up of sinusoids contains numerous ECs. These ECs express large amounts of E-selectin and VCAM-1 and promote HSC/HSPC/LSC self-renewal. (C) Enhanced CXCR4-CD44 cooperativity can promote leukemic cell survival via mTOR and elevates glycolytic influx. Metabolic stress further increases AMPK activity promoting glycolysis and Hif-1α expression. High amounts of Hif-1α create a hypoxic environment followed by release of ROS. Abbreviations: HSC/HSPC, hematopoietic stem cell/hematopoietic stem and progenitor cell; LSC, leukemic stem cell; MSC, mesenchymal stem cell; EC, endothelial cell; VCAM-1, vascular cell-adhesion molecule-1; HA, hyaluronic acid; CXCL12, C-X-C Motif Chemokine Ligand 12; PSGL-1, P-selectin glycoprotein ligand-1; CXCR4, CXC receptor 4; mTOR, mammalian target of rapamycin complex; AMPK, adenosine-5′-monophosphate-activated protein kinase; Hif-1α, hypoxia-inducible factor α; ROS, reactive oxygen species.