Metabolism, proteostasis, and signaling together regulate the balance of growth, quiescence, and cell survival in LSCs. Both cell-intrinsic (light pink background) and -extrinsic bone marrow niche factors (dark pink background) are able to influence a range of effects on LSCs, contributing to antiapoptotic and drug resistance promoting signaling. Dashed lines indicate mechanisms known to have subtype-specific regulation; solid lines indicate mechanisms for which no subtype-specific regulation known at this time. ER, endoplasmic reticulum; OXPHOS, oxidative phosphorylation.