MEMBRANE CD22 DEFINES CIRCULATING MYELOMA-RELATED CELLS AS MATURE OR LATER B-CELLS

Circulating clonally related earlier cells are present in multiple mye loma (MM) and may be involved in the dissemination of this disease, it s recurrence, and chemoresistance. The nature, stage of differentiatio n, and size of this cell population remain uncertain. Unlike other B-c ell markers, CD22 membrane expression is limited to the late different iation stages comprised between mature B cells (CD22(+)) and plasma ce lls (PC; CD22(-)) and may thus be useful in delimiting the maturationa l state of circulating early myeloma cells. Peripheral blood clone-rel ated cells were detected by anti-idiotypic (Id) monoclonal antibodies and found to express CD22 (92% to 95%), monotypic light and heavy chai n (100%), and CD38 (45%), whereas bone marrow PC were CD22-negative. C D22 expression was also documented on functional myeloma PC precursors , defined as peripheral blood cells capable of in vitro cytokine-drive n monotypic PC differentiation, because up to approximately 70% inhibi tion of this process was obtained in 10 myeloma patients through the u se of bispecific antibodies (BsAb) that deliver the plant toxin sapori n to CD22(+) cells. As further evidence of CD22 on circulating abnorma l cells, it was found that in the only patient analyzed for DNA conten t, a portion of the peripheral blood CD22(+) cells killed were hyperdi ploid. Collectively, these findings indicate that most peripheral bloo d myeloma PC precursors are mature or later B cells presenting membran e CD22. The pattern of CD22 expression suggests the existence in MM of a differentiation process analogous to the normal antigenic response, in which CD22(+) B cells migrate to the bone marrow and lose CD22 wit h PC differentiation. In addition, the sensitivity of myeloma PC precu rsors to the cytotoxic effects of the anti-CD22 BsAb and the possibili ty of interfering with their differentiation have potential therapeuti c relevance.