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. 1998 Jun;152(6):1655–1665.

Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma.

M Ocqueteau 1, A Orfao 1, J Almeida 1, J Bladé 1, M González 1, R García-Sanz 1, C López-Berges 1, M J Moro 1, J Hernández 1, L Escribano 1, D Caballero 1, M Rozman 1, J F San Miguel 1
PMCID: PMC1858455  PMID: 9626070

Abstract

Although the immunophenotype of plasma cells (PCs) from multiple myeloma (MM) patients has been extensively explored, information on the phenotypic characteristics of PCs in monoclonal gammopathy of undetermined significance (MGUS) patients is scanty and frequently controversial. Thus, the question of whether or not PCs are phenotypically different in the two disorders and whether this criteria could be useful for the differential diagnosis between MGUS and MM remains to be explored. In the present study, the immunophenotypic profile of bone marrow PCs (BMPCs) from a group of 76 MGUS patients has been analyzed by flow cytometry and compared with that of BMPCs present in both MM patients (n = 65) and control subjects (n = 10). For that purpose, a large panel of monoclonal antibodies against PC-related antigens was used together with a sensitive methodology in which a minimum of 10(3) PCs were studied. In all MGUS cases studied, two clearly defined and distinct PC subpopulations could be identified. One PC subpopulation, population A (33 +/- 31% of total PCs), constantly displayed a high CD38 expression with low forward light scatter (FSC)/side light scatter (SSC) and was positive for CD19 and negative for CD56 (only a small proportion of these PCs were weakly positive for CD56). The other PC subpopulation, population B (67 +/- 31% of total PCs), showed the opposite pattern; the antigen CD56 was strongly positive and CD19 was constantly negative, and it showed a lower CD38 expression and higher FSC/SSC values than population A. Clonality studies (cytoplasmic light chain restriction, DNA content studies, and polymerase chain reaction assessment) confirmed the clonal nature of PCs from population B and the polyclonal origin of PCs from population A. Moreover, the polyclonal PCs from MGUS displayed a phenotypic profile identical to that found in PCs from healthy individuals. By contrast, clonal PCs from all MGUS patients displayed a similar antigenic profile to myelomatous PCs, with clear phenotypic differences with respect to normal PCs: lower intensity of CD38 expression and a variable reactivity for markers that were not expressed in normal PCs, such as CD28, CD117, and sIg. Although the presence of residual polyclonal PCs was a constant finding in MGUS patients, it was a rare event in MM and, when present (only 22% of MM cases), its frequency was significantly lower than that observed in MGUS (0.25% versus 32.9%, respectively; P < 0.0001). Only 1.5% of patients with MM had more than 3% of normal PCs, whereas 98% of patients with MGUS had more than 3%. Moreover, as shown by multivariate analysis, the number of residual polyclonal PCs was the most powerful single parameter for the discrimination between MGUS and MM patients at diagnosis, even when only stage I MM cases were considered.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguzzi F., Bergami M. R., Gasparro C., Bellotti V., Merlini G. Occurrence of monoclonal components in general practice: clinical implications. Eur J Haematol. 1992 Apr;48(4):192–195. doi: 10.1111/j.1600-0609.1992.tb01584.x. [DOI] [PubMed] [Google Scholar]
  2. Ahsmann E. J., Lokhorst H. M., Dekker A. W., Bloem A. C. Lymphocyte function-associated antigen-1 expression on plasma cells correlates with tumor growth in multiple myeloma. Blood. 1992 Apr 15;79(8):2068–2075. [PubMed] [Google Scholar]
  3. Barker H. F., Hamilton M. S., Ball J., Drew M., Franklin I. M. Expression of adhesion molecules LFA-3 and N-CAM on normal and malignant human plasma cells. Br J Haematol. 1992 Jul;81(3):331–335. doi: 10.1111/j.1365-2141.1992.tb08236.x. [DOI] [PubMed] [Google Scholar]
  4. Bergsagel P. L., Smith A. M., Szczepek A., Mant M. J., Belch A. R., Pilarski L. M. In multiple myeloma, clonotypic B lymphocytes are detectable among CD19+ peripheral blood cells expressing CD38, CD56, and monotypic Ig light chain. Blood. 1995 Jan 15;85(2):436–447. [PubMed] [Google Scholar]
  5. Billadeau D., Van Ness B., Kimlinger T., Kyle R. A., Therneau T. M., Greipp P. R., Witzig T. E. Clonal circulating cells are common in plasma cell proliferative disorders: a comparison of monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, and active myeloma. Blood. 1996 Jul 1;88(1):289–296. [PubMed] [Google Scholar]
  6. Blade J., Lopez-Guillermo A., Rozman C., Cervantes F., Salgado C., Aguilar J. L., Vives-Corrons J. L., Montserrat E. Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance. Br J Haematol. 1992 Jul;81(3):391–394. doi: 10.1111/j.1365-2141.1992.tb08245.x. [DOI] [PubMed] [Google Scholar]
  7. Bottaro M., Berti E., Biondi A., Migone N., Crosti L. Heteroduplex analysis of T-cell receptor gamma gene rearrangements for diagnosis and monitoring of cutaneous T-cell lymphomas. Blood. 1994 Jun 1;83(11):3271–3278. [PubMed] [Google Scholar]
  8. Corradini P., Ladetto M., Inghirami G., Boccadoro M., Pileri A. N- and K-ras oncogenes in plasma cell dyscrasias. Leuk Lymphoma. 1994 Sep;15(1-2):17–20. doi: 10.3109/10428199409051673. [DOI] [PubMed] [Google Scholar]
  9. Drach J., Gattringer C., Huber H. Expression of the neural cell adhesion molecule (CD56) by human myeloma cells. Clin Exp Immunol. 1991 Mar;83(3):418–422. doi: 10.1111/j.1365-2249.1991.tb05654.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fend F., Weyrer K., Drach J., Schwaiger A., Umlauft F., Grünewald K. Immunoglobulin gene rearrangement in plasma cell dyscrasias: detection of small clonal cell populations in peripheral blood and bone marrow. Leuk Lymphoma. 1993 Jun;10(3):223–229. doi: 10.3109/10428199309145887. [DOI] [PubMed] [Google Scholar]
  11. Goodeve A. C., Tagariello G., Chuansumrit A., Preston F. E., Peake I. R. A rapid and cost effective method for analysis of dinucleotide repeat polymorphisms in the factor VIII gene. Blood Coagul Fibrinolysis. 1996 Oct;7(7):672–677. doi: 10.1097/00001721-199610000-00002. [DOI] [PubMed] [Google Scholar]
  12. Harada H., Kawano M. M., Huang N., Harada Y., Iwato K., Tanabe O., Tanaka H., Sakai A., Asaoku H., Kuramoto A. Phenotypic difference of normal plasma cells from mature myeloma cells. Blood. 1993 May 15;81(10):2658–2663. [PubMed] [Google Scholar]
  13. Harada Y., Kawano M. M., Huang N., Mahmoud M. S., Lisukov I. A., Mihara K., Tsujimoto T., Kuramoto A. Identification of early plasma cells in peripheral blood and their clinical significance. Br J Haematol. 1996 Jan;92(1):184–191. doi: 10.1046/j.1365-2141.1996.300835.x. [DOI] [PubMed] [Google Scholar]
  14. Kawano M. M., Mihara K., Tsujimoto T., Huang N., Kuramoto A. A new phenotypic classification of bone marrow plasmacytosis. Int J Hematol. 1995 Jun;61(4):179–188. doi: 10.1016/0925-5710(95)00363-w. [DOI] [PubMed] [Google Scholar]
  15. Kyle R. A. "Benign" monoclonal gammopathy--after 20 to 35 years of follow-up. Mayo Clin Proc. 1993 Jan;68(1):26–36. doi: 10.1016/s0025-6196(12)60015-9. [DOI] [PubMed] [Google Scholar]
  16. Kyle R. A. Diagnostic criteria of multiple myeloma. Hematol Oncol Clin North Am. 1992 Apr;6(2):347–358. [PubMed] [Google Scholar]
  17. Kyle R. A. Monoclonal gammopathy of undetermined significance (MGUS). Baillieres Clin Haematol. 1995 Dec;8(4):761–781. doi: 10.1016/s0950-3536(05)80258-6. [DOI] [PubMed] [Google Scholar]
  18. Kyle R. A. Monoclonal gammopathy of undetermined significance and solitary plasmacytoma. Implications for progression to overt multiple myeloma. Hematol Oncol Clin North Am. 1997 Feb;11(1):71–87. doi: 10.1016/s0889-8588(05)70416-0. [DOI] [PubMed] [Google Scholar]
  19. Leo R., Boeker M., Peest D., Hein R., Bartl R., Gessner J. E., Selbach J., Wacker G., Deicher H. Multiparameter analyses of normal and malignant human plasma cells: CD38++, CD56+, CD54+, cIg+ is the common phenotype of myeloma cells. Ann Hematol. 1992 Mar;64(3):132–139. doi: 10.1007/BF01697400. [DOI] [PubMed] [Google Scholar]
  20. Linke B., Bolz I., Pott C., Hiddemann W., Kneba M. Use of UITma DNA polymerase improves the PCR detection of rearranged immunoglobulin heavy chain CDR3 junctions. Leukemia. 1995 Dec;9(12):2133–2137. [PubMed] [Google Scholar]
  21. Mathew P., Ahmann G. J., Witzig T. E., Roche P. C., Kyle R. A., Greipp P. R. Clinicopathological correlates of CD56 expression in multiple myeloma: a unique entity? Br J Haematol. 1995 Jun;90(2):459–461. doi: 10.1111/j.1365-2141.1995.tb05175.x. [DOI] [PubMed] [Google Scholar]
  22. Orfäo A., García-Sanz R., López-Berges M. C., Belén Vidriales M., González M., Caballero M. D., San Miguel J. F. A new method for the analysis of plasma cell DNA content in multiple myeloma samples using a CD38/propidium iodide double staining technique. Cytometry. 1994 Dec 1;17(4):332–339. doi: 10.1002/cyto.990170409. [DOI] [PubMed] [Google Scholar]
  23. Pellat-Deceunynck C., Barillé S., Puthier D., Rapp M. J., Harousseau J. L., Bataille R., Amiot M. Adhesion molecules on human myeloma cells: significant changes in expression related to malignancy, tumor spreading, and immortalization. Cancer Res. 1995 Aug 15;55(16):3647–3653. [PubMed] [Google Scholar]
  24. Pellat-Deceunynck C., Bataille R., Robillard N., Harousseau J. L., Rapp M. J., Juge-Morineau N., Wijdenes J., Amiot M. Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood. 1994 Oct 15;84(8):2597–2603. [PubMed] [Google Scholar]
  25. Ruiz-Argüelles G. J., San Miguel J. F. Cell surface markers in multiple myeloma. Mayo Clin Proc. 1994 Jul;69(7):684–690. doi: 10.1016/s0025-6196(12)61350-0. [DOI] [PubMed] [Google Scholar]
  26. San Miguel J. F., Garcia-Sanz R., Gonzalez M., Orfao A. Immunophenotype and DNA cell content in multiple myeloma. Baillieres Clin Haematol. 1995 Dec;8(4):735–759. doi: 10.1016/s0950-3536(05)80257-4. [DOI] [PubMed] [Google Scholar]
  27. Sonneveld P., Durie B. G., Lokhorst H. M., Frutiger Y., Schoester M., Vela E. E. Analysis of multidrug-resistance (MDR-1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma. Br J Haematol. 1993 Jan;83(1):63–67. doi: 10.1111/j.1365-2141.1993.tb04632.x. [DOI] [PubMed] [Google Scholar]
  28. Van Camp B., Durie B. G., Spier C., De Waele M., Van Riet I., Vela E., Frutiger Y., Richter L., Grogan T. M. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood. 1990 Jul 15;76(2):377–382. [PubMed] [Google Scholar]
  29. Zandecki M., Facon T., Bernardi F., Izydorczyk V., Dupond L., François M., Reade R., Iaru T., Bauters F., Cosson A. CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance. J Clin Pathol. 1995 Jun;48(6):548–552. doi: 10.1136/jcp.48.6.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. van Zaanen H. C., Vet R. J., de Jong C. M., von dem Borne A. E., van Oers M. H. A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry. Br J Haematol. 1995 Sep;91(1):55–59. doi: 10.1111/j.1365-2141.1995.tb05244.x. [DOI] [PubMed] [Google Scholar]

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