Unraveling the contribution of ectoenzymes to myeloma life and survival in the bone marrow niche.

Thebonemarrowprovidesaprotectedenvironmentforgeneratingavastarrayofcelltypes.Bonesarethusadynamic sourceofstructuralcomponentsandsolublefactorsusedeitherlocallyoratadistancefromtheirsiteofproduction. We discuss the role of ectoenzymes in the bone niche where human myeloma grows. Selected ectoenzymes have been tested for their ability to promote production of substrates involved in signaling, synthesis of growth factors and hormones, and modulation of the immune response. Because of the difficulty of simultaneously tracking all these activities, we narrow our focus to events potentially influencing synthesis of adenosine (ADO), an important regulator of multiple biological functions, including local immunological tolerance. Our working hypothesis, to be discussed and partially tested herein, is that CD38, and likely BST1/CD157—both NAD+-consuming enzymes, are activeinthemyelomanicheandleadadiscontinuouschainofectoenzymeswhosefinalproductsareexploitedbythe neoplastic plasma cell as part of its local survival strategy. Coadjuvant ectoenzymes include PC-1/CD203a, CD39, and CD73, which control the production of ADO. Results discussed here and from ongoing experiments indicate that the myeloma niche hosts the canonical, as well as alternative, pathways of ADO generation. Other possibilities are presented and discussed.