Identification of immature and mature myeloma cells in the bone marrow of human myelomas

Abstract

With regard to the expression of adhesion molecules, human myeloma cells freshly isolated from bone marrow were heterogeneous. By two- color analysis with anti-VLA-5 antibody (PE staining) and FITC-labeled anti-CD38 antibody, we found all myeloma cells located at CD38-strong positive (CD38++) fraction and identified two subpopulations among these myeloma cells: CD38++ VLA-5-(VLA-5-) myeloma cells and CD38++ VLA- 5+ (VLA-5+) myeloma cells. To clarify the biologic character of these two subpopulations, the morphology, in vitro proliferative activity and in vitro M-protein secretion were examined in each fraction isolated by the purification procedure or a cell sorter. Morphologic examination showed that VLA-5- myeloma cells were mostly immature or plasmablastic and VLA-5+ cells were mature myeloma cells. Furthermore, VLA-5- myeloma cells proliferated markedly in vitro and responded to interleukin 6 (IL- 6), a growth factor for myeloma cells, while VLA-5+ myeloma cells showed very low uptakes of 3H-thymidine and no responses to IL-6 but secreted higher amounts of M-protein (immunoglobulin) in vitro significantly. Therefore, we could clarify here heterogeneity of human myeloma cells in the bone marrow with regard to the expression of VLA- 5, one of integrin adhesion molecules; VLA-5- myeloma cells were proliferative immature cells and VLA-5+ cells were mature myeloma cells.

Cyclin D1 and p16INK4A are preferentially expressed in immature and mature myeloma cells, respectively

“…Recent phenotypic analysis clearly showed that myeloma cells are heterogenous, and that immature, intermediate and mature myeloma cells are found in the bone marrow (BM) of myeloma patients (Greipp et al, 1985;Kawano et al, 1993). Biological investigations confirmed that immature myeloma cells were proliferative cells, but mature myeloma cells were resting cells .…”

Generation of polyclonal plasmablasts from peripheral blood B cells: a normal counterpart of malignant plasmablasts

“…29 CD20 Ϫ /CD38 ϩϩ cells lacked CD49e and expressed CD45 and CD95, as previously reported for tonsillar plasma cells and plasma cells from RP, unlike normal bone marrow plasma cells and mature myeloma cells (Table 2). 21,25,26,28,30 Moreover, CD138, the only differentiation antigen to distinguish plasma cells from plasmablasts, 21 was expressed on only 13.7% Ϯ 4.4% (n ϭ 6) of day 6 polyclonal CD20 Ϫ /CD38 ϩϩ cells ( Figure 3C), unlike CD20 ϩ /CD 38 Ϫ cells that did not express CD138. Similarly, only 17% of plasma cells from RP are CD138 ϩ .…”

Clinical significance of granule‐containing myeloma cells in patients with newly diagnosed multiple myeloma

“…CD49e is very late activation antigen-5 (VLA-5), which is a member of a family of heterodimeric transmembrane proteins that belong to the integrin family and plays an important role as a cell adhesion molecule [31]. Kawano et al [39] reported that VLA-5-negative myeloma cells were proliferative, IL-6-responsive immature cells. In contrast, VLA-5-positive myeloma cells were non proliferative, mature myeloma cells, non-responsive to IL-6 and secreted higher amounts of M-protein than VLA-5-negative myeloma cells.…”