Increasing interest has been expressed for flow cytometric immunophenotyping for diagnosis and monitoring in plasma cell dyscrasias over the last decades. The aim of this investigation was to compare the expression strength of various cell surface markers used traditionally or currently under investigation on normal and abnormal PC populations. We enrolled 295 consecutive patients undergoing bone marrow aspiration in the workup of monoclonal gammopathies, selecting 54 normal and 241 abnormal PC populations via flow cytometry to characterize the expression of CD45, CD38, CD138, CD19, CD56, CD20, CD27, CD28, CD81, CD117 and CD200 on the cell surface of PCs. We observed significant differences in the expression strength of all assessed markers between normal and abnormal PC populations in all markers except for CD20. While none of them was conclusive on its own, the combination of CD81 positivity and CD117 negativity was present in 98.1% of normal PC populations tested. In contrast, particularly CD117 positivity, but also CD81 negativity was indicative of an abnormal PC phenotype. Our results highlight the descriptive value of CD81 and CD117 for the allocation of bone marrow PCs to a normal or abnormal phenotype.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Monoclonal gammopathy of undetermined significance
- NK cell:
Natural killer cell
Kyle RA, Rajkumar SV (2004) Multiple myeloma. N Engl J Med 18:1860–1873
Rajkumar SV (2013) Multiple myeloma: 2013 update on diagnosis, risk-stratification, and management. Am J Hematol 3:226–235
Chesi M, Bergsagel PL (2013) Molecular pathogenesis of multiple myeloma: basic and clinical updates. Int J Hematol 3:313–323
Raja KR, Kovarova L, Hajek R (2010) Review of phenotypic markers used in flow cytometric analysis of MGUS and MM, and applicability of flow cytometry in other plasma cell disorders. Br J Haematol 3:334–351
Palumbo A, Anderson K (2011) Multiple myeloma. N Engl J Med 11:1046–1060
Kyle RA, Rajkumar SV (2008) Multiple myeloma. Blood 6:2962–2972
Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC (2009) Multiple myeloma. Lancet 9686:324–339
Willrich MA, Katzmann JA (2016) Laboratory testing requirements for diagnosis and follow-up of multiple myeloma and related plasma cell dyscrasias. Clin Chem Lab Med 6:907–919
Paiva B, Almeida J, Perez-Andres M, Mateo G, Lopez A, Rasillo A et al (2010) Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytom B Clin Cytom 4:239–252
Tran DN, Smith SA, Brown DA, Parker AJ, Joseph JE, Armstrong N et al (2017) Polychromatic flow cytometry is more sensitive than microscopy in detecting small monoclonal plasma cell populations. Cytom B Clin Cytom 2:136–144
Rawstron AC, Orfao A, Beksac M, Bezdickova L, Brooimans RA, Bumbea H et al (2008) Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 3:431–438
Paiva B, Vidriales MB, Rosinol L, Martinez-Lopez J, Mateos MV, Ocio EM et al (2013) A multiparameter flow cytometry immunophenotypic algorithm for the identification of newly diagnosed symptomatic myeloma with an MGUS-like signature and long-term disease control. Leukemia 10:2056–2061
Ocqueteau M, Orfao A, Almeida J, Blade J, Gonzalez M, Garcia-Sanz R et al (1998) Immunophenotypic characterization of plasma cells from monoclonal gammopathy of undetermined significance patients. Implications for the differential diagnosis between MGUS and multiple myeloma. Am J Pathol 6:1655–1665
Kobayashi S, Hyo R, Amitani Y, Tanaka M, Hashimoto C, Sakai R et al (2006) Four-color flow cytometric analysis of myeloma plasma cells. Am J Clin Pathol 6:908–915
Harada H, Kawano MM, Huang N, Harada Y, Iwato K, Tanabe O et al (1993) Phenotypic difference of normal plasma cells from mature myeloma cells. Blood 10:2658–2663
Robillard N, Avet-Loiseau H, Garand R, Moreau P, Pineau D, Rapp MJ et al (2003) CD20 is associated with a small mature plasma cell morphology and t(11;14) in multiple myeloma. Blood 3:1070–1071
Zandecki M, Facon T, Bernardi F, Izydorczyk V, Dupond L, Francois M et al (1995) CD19 and immunophenotype of bone marrow plasma cells in monoclonal gammopathy of undetermined significance. J Clin Pathol 6:548–552
Guikema JE, Hovenga S, Vellenga E, Conradie JJ, Abdulahad WH, Bekkema R et al (2003) CD27 is heterogeneously expressed in multiple myeloma: low CD27 expression in patients with high-risk disease. Br J Haematol 1:36–43
Katayama Y, Sakai A, Oue N, Asaoku H, Otsuki T, Shiomomura T et al (2003) A possible role for the loss of CD27–CD70 interaction in myelomagenesis. Br J Haematol 2:223–234
Pellat-Deceunynck C, Bataille R, Robillard N, Harousseau JL, Rapp MJ, Juge-Morineau N et al (1994) Expression of CD28 and CD40 in human myeloma cells: a comparative study with normal plasma cells. Blood 8:2597–2603
Robillard N, Jego G, Pellat-Deceunynck C, Pineau D, Puthier D, Mellerin MP et al (1998) CD28, a marker associated with tumoral expansion in multiple myeloma. Clin Cancer Res 6:1521–1526
Ocqueteau M, Orfao A, Garcia-Sanz R, Almeida J, Gonzalez M, San Miguel JF (1996) Expression of the CD117 antigen (c-Kit) on normal and myelomatous plasma cells. Br J Haematol 3:489–493
Bataille R, Pellat-Deceunynck C, Robillard N, Avet-Loiseau H, Harousseau JL, Moreau P (2008) CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis. Leuk Res 3:379–382
Lin P, Owens R, Tricot G, Wilson CS (2004) Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 4:482–488
Olteanu H, Harrington AM, Hari P, Kroft SH (2011) CD200 expression in plasma cell myeloma. Br J Haematol 3:408–411
Paiva B, Gutierrez NC, Chen X, Vidriales MB, Montalban MA, Rosinol L et al (2012) Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients. Leukemia 8:1862–1869
Flores-Montero J, de Tute R, Paiva B, Perez JJ, Bottcher S, Wind H et al (2016) Immunophenotype of normal vs. myeloma plasma cells: toward antibody panel specifications for MRD detection in multiple myeloma. Cytom B Clin Cytom 1:61–72
Porwit A (2013) Immunophenotyping of selected hematologic disorders–focus on lymphoproliferative disorders with more than one malignant cell population. Int J Lab Hematol. 3:275–282
Cannizzo E, Carulli G, Del Vecchio L, Ottaviano V, Bellio E, Zenari E et al (2012) The role of CD19 and CD27 in the diagnosis of multiple myeloma by flow cytometry: a new statistical model. Am J Clin Pathol 3:377–386
Flanders A, Stetler-Stevenson M, Landgren O (2013) Minimal residual disease testing in multiple myeloma by flow cytometry: major heterogeneity. Blood 6:1088–1089
Bataille R, Jego G, Robillard N, Barille-Nion S, Harousseau JL, Moreau P et al (2006) The phenotype of normal, reactive and malignant plasma cells. Identification of “many and multiple myelomas” and of new targets for myeloma therapy. Haematologica 9:1234–1240
Pellat-Deceunynck C, Bataille R (2004) Normal and malignant human plasma cells: proliferation, differentiation, and expansions in relation to CD45 expression. Blood Cells Mol Dis 2:293–301
Robillard N, Pellat-Deceunynck C, Bataille R (2005) Phenotypic characterization of the human myeloma cell growth fraction. Blood 12:4845–4848
Moreau P, Robillard N, Jego G, Pellat C, Le Gouill S, Thoumi S et al (2006) Lack of CD27 in myeloma delineates different presentation and outcome. Br J Haematol 2:168–170
Cannizzo E, Bellio E, Sohani AR, Hasserjian RP, Ferry JA, Dorn ME et al (2010) Multiparameter immunophenotyping by flow cytometry in multiple myeloma: The diagnostic utility of defining ranges of normal antigenic expression in comparison to histology. Cytom B Clin Cytom 4:231–238
Tohami T, Drucker L, Shapiro H, Radnay J, Lishner M (2007) Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential. FASEB J 3:691–699
Barrena S, Almeida J, Yunta M, Lopez A, Fernandez-Mosteirin N, Giralt M et al (2005) Aberrant expression of tetraspanin molecules in B-cell chronic lymphoproliferative disorders and its correlation with normal B-cell maturation. Leukemia 8:1376–1383
Luo RF, Zhao S, Tibshirani R, Myklebust JH, Sanyal M, Fernandez R et al (2010) CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas. Hum Pathol 2:271–280
Tembhare PR, Yuan CM, Venzon D, Braylan R, Korde N, Manasanch E et al (2014) Flow cytometric differentiation of abnormal and normal plasma cells in the bone marrow in patients with multiple myeloma and its precursor diseases. Leuk Res 3:371–376
Alapat D, Coviello-Malle J, Owens R, Qu P, Barlogie B, Shaughnessy JD et al (2012) Diagnostic usefulness and prognostic impact of CD200 expression in lymphoid malignancies and plasma cell myeloma. Am J Clin Pathol 1:93–100
Olteanu H, Harrington AM, Kroft SH (2012) CD200 expression in plasma cells of nonmyeloma immunoproliferative disorders: clinicopathologic features and comparison with plasma cell myeloma. Am J Clin Pathol 6:867–876
Moreaux J, Hose D, Reme T, Jourdan E, Hundemer M, Legouffe E et al (2006) CD200 is a new prognostic factor in multiple myeloma. Blood 13:4194–4197
Conflict of interest
The authors declare they have no conflict of interest with respect to the present manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Draxler, D.F., Wutzlhofer, L.M., Slavka, G. et al. Flow Cytometric Evaluation of Traditional and Novel Surface Markers for the Diagnosis of Plasma Cell Dyscrasias. Indian J Hematol Blood Transfus 35, 673–682 (2019). https://doi.org/10.1007/s12288-019-01105-w
- Multiple myeloma
- Plasma cell dyscrasias
- Plasma cells
- Flow cytometry