The functional sequelae of the immunosuppressive BM microenvironment are diminished effector T-cell survival, proliferation, and function, evidenced by multiple CD4 and CD8 T-cell signaling defects (e.g., downregulation of CD28, CD152, CD3ζ, p56lck, ZAP-70, and PI3K; upregulation of exhaustion markers) in patients with advanced stage MM [110]. The gene discussed is CD28; the disease is Miyoshi myopathy.