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Figure 2. Causes and consequences of autophagy in MM cells within BMME. In the bone marrow, stromal cells secrete IL-6, VEGF, and IGF-1 due to intercellular interactions with MM cells. IL-6 stimulates UPR and autophagy through XBP-1. Apoptosis triggers autophagy via the JAK/STAT3 and MAPK/ERK pathways or IL-6. Autophagy and survival are promoted by the interaction of BCMA and APRIL through NF-κB and XBP-1. Adhesion molecules such as TNF-α, ICAM-1, LFA-1, and VLA-4 develop drug resistance by inducing autophagy via NF-κB. PI3K/AKT/mTOR inhibition promotes autophagy in drug-resistant cells. UPR upregulates HIF1-α through XBP-1 processing, which triggers autophagy through AMPK and mTOR. BMME: Bone marrow microenvironment; MM: multiple myeloma; UPR: unfolded protein response.