We furthermore suggest that a competitive flux, or equilibrium, between BM-resident CD69+ TTE and circulating CD69- TTE regulates the egress of myeloma-reactive CD69- TTE from the BM to PB and contributes to senescence (CD69-PD-1lo TTE) or exhaustion (CD69+PD-1hi TTE) of CD8+ TTE. The gene discussed is CD8A; the disease is plasma cell myeloma.