Segregation of precursors with high proliferative potential from their differentiated progeny in a myeloma cell line

Human myeloma colonies were grown from the peripheral blood of a patient with multiple myeloma who was unresponsive to any further therapy. The majority of primary myeloma colonies contained cells that were able to form secondary colonies upon replating and facilitated the establishment of a myeloma cell line (OCI-My5). The recloning procedure was repeated for colonies that contained the highest and lowest number of clonogenic progenitors. This approach allowed the selection of clonogenic cells with high self-renewal potential. Using a cell separation procedure based on differences in sedimentation velocity, clonogenic myeloma cells with high self-renewal were found to be smaller than the majority of clonogenic myeloma cells. Furthermore, cells with increasing size did not only display reduced self-renewal ability but showed significant increases in the content of mRNA transcripts for lambda light chains. These data were consistent with the view that clonogenic myeloma cells are heterogeneous with respect to self-replication and that they give rise to more differentiated progeny, as documented by increasing mRNA levels for the M-protein.