In this mini-review, in the context of earlier published data, we discussed our recent data which suggest that the host-myeloma escape stage clinically defined by progression from MGUS to MM is characterized by lessening involvement of Treg in suppressive CD39/CD73 adenosine pathway and development of the regulatory mechanism between BM-resident CD69+ TTE and their circulating CD69- TTE counterpart encompassing oligoclonal expanded TTE. Here, NT5E is linked to plasma cell myeloma.