The presence of circulating clonal CD19+ cells in multiple myeloma.
Multiple myeloma (MM) is a B-cell malignancy characterized by the expansion of mature plasma cells (PC) localized in the bone marrow (BM). Several studies have identified circulating clonotypic CD19+ cells at a differentiation stage preceding the PC. The level of circulating clonotypic CD19+ cells is highly variable but generally low. Circulating clonotypic cells respond well to induction therapy, although a small subset within the CD19 compartment is resistant even to high-dose chemotherapy. The clonal CD19+ cells represent an ongoing differentiating population ranging from memory B-cells to plasmablasts. However, a clonal relationship gives no proof of malignant potential, and whether or not clonotypic precursor cells are involved in the disease process is a subject of intense debate. Translocations involving the immunoglobulin locus (14q32) are an early non-transforming event common to both monoclonal gammopathy of undetermined significance (MGUS) and MM introduced at the memory B-cell level. At the plasmablast stage, a phenotypic transformation occurs with downregulation of CD19 and upregulation of myeloma specific markers such as CD56, CD117 and CD28. Translocations involving the isotype-switch machinery and the introduction of tumor-specific markers at the plasmablast stage suggest that the clonal CD19+ memory B-cells and CD19+ plasmablasts are non-malignant, but immortalized relatives that gave rise to myeloma. A final proof of the malignant potential of CD19+ clonotypic cells might await the identification of the molecular events causing the transformation in myeloma.
Rasmussen
T
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Department of Hematology L, Herlev Hospital, University of Copenhagen, Herlev, Denmark. thra@herlevhosp.kbhamt.dk
D018941:Antigens, CD19 / Q000032:analysis*; D018952:Antigens, CD34 / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation; D002999:Clone Cells / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology; D009101:Multiple Myeloma / Q000276:immunology* / Q000473:pathology; D010950:Plasma Cells / Q000502:physiology; D016133:Polymerase Chain Reaction
D018941:Antigens, CD19; D018952:Antigens, CD34