THE BONE-MARROW OF MULTIPLE-MYELOMA PATIENTS CONTAINS B-CELL POPULATIONS AT DIFFERENT STAGES OF DIFFERENTIATION THAT ARE CLONALLY RELATED TO THE MALIGNANT PLASMA-CELL

One of the distinguishing features of multiple myeloma (MM) is the pro liferation of a clonal plasma cell population in the bone marrow (BM). It is of particular interest that the tumor plasma cells appear to be restricted to the microenvironment of the BM and are rarely detected in the peripheral system, yet the disease is found widely disseminated throughout the axial skeleton. Furthermore, isolation of MM tumor cel l lines has proven to be quite problematic due to their slow growth ra te. These observations have instigated the search for earlier cells in the B cell lineage that are clonally related to the plasma cell tumor and that may represent the growth fraction of the tumor. We used alle le-specific oligonucleotides (ASO) derived from the third complementar ity determining region of the rearranged tumor immunoglobulin heavy ch ain gene to detect isotypes clonally related to the plasma cell tumor. By reverse transcribing RNA from the BM with a panel of CH primers (m u, delta, alpha, and gamma), followed by ASO-polymerase chain reaction amplification, we demonstrate the existence of preswitch isotype spec ies that are clonally related to the myeloma tumor. Furthermore, we sh ow that separation of the BM cells into CD45+ and CD38+ cell populatio ns results in a lineage-specific expression of the clonally related RN A molecules, with the Cmu and Cdelta in the CD45+, and Cgamma in the C D38+ population. Interestingly, clonally related Calpha transcripts ar e also derived from the CD45+ fraction. These results confirm the pres ence of B cell populations clonally related to the plasma cell tumor a nd are consistent with models that propose the existence of myeloma pr ecursors.