CD82 mediates leukemic stem cell survival and interactions with the microenvironment. CD82 mediates leukemic stem cell (LSC) interaction with the BM in multiple ways. It increases microenvironment interaction by organizing N-cadherin at the cell surface in high densities via CD82 palmitoylation (green triangles) and glycosylation (red spheres). However, the connection of N-cadherin to CD82-associated intracellular effects is still unknown. CD82-associated STAT5 signaling can combine with increased p-Akt (via inhibition of PTEN by DNA methylation from EZH2 due to downregulation of p38 caused by CD82-associated signaling) to increase the expression of antiapoptotic protein BCL2L12. The combination of these effects leads to increased LSC survival.