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

Kawano, Michio; Huang, Naihui; Harada, Hironori; Harada, Yuka; Sakai, Akira; Tanaka, Hideo; Iwato, K; Kuramoto, Atsushi

doi:10.1182/blood.v82.2.564.564

Cited by 129 publications

(23 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The presence of morphologically primitive plasma cells in the bone marrow of patients with myeloma has been determined as a poor prognostic factor by the German Cooperative Study Group (Sailor et al, 1995). The phenotype of these cells has been defined by a number of workers as CD38 , CD45+, CD19+, VLA-5 ÿ ( Jensen et al, 1991;Omede et al, 1993;Kawano et al, 1993). In order to improve the sensitivity of the LI and to investigate the significance of the LI of plasma cell subpopulations, we have introduced a flow cytometric CD38 LI assay and have used dual CD38 and CD45 expression to evaluate the clinical significance of the LI of plasma cell subpopulations ( Jensen et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

et al. 1996

View full text Add to dashboard Cite

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38++) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38++ population was significantly higher (2.7 +/- 0.4%) than the LI determined by the traditional slide technique (0.6 +/- 0.1%) for 65 samples tested. Primitive plasma cells (CD38++, CD45++) had a higher labelling index than mature plasma cells (CD38++, CD45-) (7.0 +/- 1.3% v 1.8% +/- 0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2 +/- 2.9% v 2.2 +/- 0.7%; z = 19.9, P < 0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.

show abstract

Section: Discussionmentioning

confidence: 99%

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

et al. 1996

View full text Add to dashboard Cite

show abstract

“…It has already been shown that CD38 þþ populations with low SSC in general consist of plasma or plasmacytoid cells (Terstappen et al, 1990;Hata et al, 1993;Kawano et al, 1993). We performed cell-sorting experiments to confirm the specific morphology and to look for morphologic differences between the two subsets.…”

Section: Morphology Of the Two Plasma Cell Subsetsmentioning

confidence: 97%

“…Staining of intracellular kappa (k) and lambda (l) light chains was performed in many cases. It is known that plasma cells are strongly CD38 positive (CD38 þþ ) (Terstappen et al, 1990;San Miguel et al, 1991;Leo et al, 1992;Kawano et al, 1993) and usually have a distinct light scatter profile (Shimazaki et al, 1990). However, investigating peripheral blood samples, this population could eventually overlap with those of activated T cells or natural killer (NK) cells.…”

mentioning

confidence: 99%

Two subsets of peripheral blood plasma cells defined by differential expression of CD45 antigen

et al. 1997

View full text Add to dashboard Cite

Summary. The purpose of this study was to optimize the flow cytometric determination of circulating normal and malignant plasma cells (PC). We investigated peripheral blood (PB) samples of 65 patients with multiple myeloma or monoclonal gammopathy of unknown significance and 47 control subjects using CD38, CD45, B-B4, CD56, VLA-4, VLA-5 and CD19 monoclonal antibodies (MoAbs). Mono-or polyclonality was determined by staining of intracellular kappa and lambda light chains. Two subpopulations of PBPC were distinguished by differential expression of CD45. CD45 positive (CD45 þ ) PC showed a more immature morphology and were detected in all groups. They were polyclonal in the control subjects and either poly-or monoclonal in the myeloma patients. In contrast, CD45 negative (CD45 ¹ ) PBPC only occurred in myeloma patients and were consistently monoclonal, their presence being significantly associated with high disease activity (P < 0·001). Although detection of CD45 ¹ PBPC using CD38 or B-B4 MoAbs lead to similar results, CD45þ PBPC often were recognized to a lesser extent by B-B4 than by CD38 MoAbs.In conclusion, normal and malignant circulating PC can reliably be identified using CD38 and CD45 MoAbs. CD45 expression separates PBPC into two subsets of which the CD45 ¹ one only occurs in myeloma patients.

show abstract

“…le, 0-These findings suggest that D2 is difl"crent from CD38 and PCA-1, and more specific to myeloma cells. Integrin receptors, which are reported to be variably expressed during the maturation of plasma cells [11], and CD45. which is expressed on immature plasma cells [12].…”

Section: Resultsmentioning

confidence: 99%

Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1

Hata

Matsuzaki

Matsuno

et al. 1994

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYA new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM). eslublished from lhe pleural efTusion and bone marrow, respectively, of the same patient. Since I2BM expresses CD20, CD38, and PCA-I antigens, while 12PE has lost CD20. 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE thun to I2BM. Thus, a clone. D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases e.xccpt one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-I expression was related to extramedullary invasion. The morphology of the myeloma eells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells.

show abstract

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

Cited by 129 publications

References 18 publications

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

Two subsets of peripheral blood plasma cells defined by differential expression of CD45 antigen

Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1

Contact Info

Product

Resources

About