The clonal hierachy in multiple myeloma.

In this report we evaluated the number and phenotype of blood circulating B-cell subsets at different stages of differentiation in 26 patients with newly diagnosed multiple myeloma (MM). In all patients, plasma cells and/or plasma blasts could be identified by flow cytometry with a mean frequency of 1.20% and 0.07%, respectively. In 76.9% of the patients these cells showed aberrant expression mainly of CD56, CD28 and CD117, none of these markers were found on the earlier B-lymphocytes. Clonal B-cells preceding the plasma blast stage were identified by patient specific IgH RT-PCR on sorted B-cell subsets. The clonal cells included the less differentiated CD38+ CD19+ and CD38-/CD19+ subsets. illustrating that the clonal cells are part of an ongoing differentiation process. Further, the presence of CD38-/CD19+ cells with somatically mutated Cgamma transcripts identical to the tumor-specific Calpha transcript, shows that the clonal hierarchy in myeloma may include memory B-cells.