Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma

Abstract

The blood of most patients with active multiple myeloma (MM) contains cells related to the bone marrow tumor. However, identifying clonal cells in the blood of patients with monoclonal gammopathy of undetermined significance (MGUS) has been difficult. In this study, we analyzed blood mononuclear cells (BMNCs) from 16 patients with MGUS, 2 with amyloidosis, 8 with smoldering MM (SMM), 2 with indolent MM (IMM), and 15 with active MM using three different methods to detect and quantitate clonal cells, ie, immunofluorescence microscopy (IM) for monoclonal plasma cells, three-color flow cytometry (FC) for CD38(+)CD45- CD45(dim) cells, and the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR). Using ASO-PCR, we were able to detect clonal cells in the blood in 13 of 16 patients with MGUS, 2 of 2 with amyloid, 6 of 8 with SMM, 2 of 2 with IMM, and 13 of 15 with MM. In 9 of the 13 patients with MGUS with blood involvement, the number of clonal cells was very small ( < 0.04% of the BMNCs). The median percentage of clonal cells as determined by ASO-PCR was 0.02 for MGUS, 0.02 for SMM, and 0.24 for MM. Clonal plasma cells or CD38+CD45- CD45(dim) cells were identified by IM or FC in 6 of 16 MGUS patients, 4 of 8 with SMM, and 11 of 15 with MM. In all cases in which IM or FC detected clonal cells, the ASO-PCR was positive. This study shows that, by using ASO-PCR, clonal cells can be found at very low levels in the blood in most patients with MGUS. However, the number of clonal cells in the blood of MGUS patients is less than those with overt MM (P = .006). In contrast to MGUS, patients with active MM are more likely to have identifiable clonal circulating plasma cells (P = .05).

Normal and clonal B lineage cells can be distinguished by their differential expression of B cell antigens and adhesion molecules in peripheral blood from multiple myeloma (MM) patients—diagnostic and clinical implications

“…As has been recently described [18], CD38 þþ CD45 ¹/dim cIg þ cells can be detected in the PB of MM patients by FCM analysis. However, their complete antigenic profile has not been determined [17,18]. Three-colour FCM analysis with the B-B4 (CD138) MoAb confirmed that all circulating CD38 þþ CD45 ¹/dim cells were positive for this antigen.…”

“…In this regard, Jensen et al [16] have speculated that circulating CD19 þ CD11b þ cells appear to represent the myeloma precursor cells. Recently, Billadeau et al [17] and Witzig et al [18] found that circulating CD38 þþ , CD45 ¹/dim expressed monotypic cytoplasmic immunoglobulin (cIg) and showed characteristic plasma cell morphology. Nevertheless, these cells were not examined for their expression of B cell antigens and adhesion molecules.…”

Primary systemic amyloidosis with delayed progression to multiple myeloma

“…Progression to multiple myeloma in these six patients might be analogous to progression of MGUS to multiple myeloma. In both MGUS and AL, circulating clonal plasma cells have been identified in the peripheral blood 10. The number of such cells in AL and MGUS is significantly less than in overt multiple myeloma.…”

Plasma Cell Leukemia – the Forgotten Disease

“…Ačkoliv se PC obvykle v periferní krvi nevyskytují, v případě ostatních MG mohou v nižším množství expandovat z KD do periferie jako cPC [9,10]. Přítomnost těchto klonálních cPC byla dokumentována u zhruba 70-84 % nově dia gnostikovaných pa cientů s MM a u > 90 % pa cientů v relapsu onemocnění [10][11][12][13][14].…”