ABSTRACT Plasma cell neoplasms comprise a spectrum of diseases that include monoclonal gammopathy of undetermined signi-ficance (MGUS) and multiple myeloma (MM). Flow cytometric immunophenotyping has become an invaluable tool as an ancillary and diagnostic test for hematologic malignancies and is being used with increasing frequency in the diag-nosis and monitoring of plasma cell neoplasms. As multiparameter flow cytometry has evolved, faster fluidics and detection systems facilitate the screening of a large number of events and the detection of multiple antigens simultaneously. This review addresses the approaches used to evaluate clonal plasma cell neoplasms and describes different surface and cytoplasmic markers and techniques that are important for the study of these diseases.
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C. Singh, S. Yohe, L. Baughn and M. Linden, "Utility of Flow Cytometry to Classify Abnormal Plasma Cell Populations in Marrow Samples Collected from Patients with Putative Plasma Cell Neoplasms," Open Journal of Blood Diseases, Vol. 2 No. 3, 2012, pp. 39-45. doi: 10.4236/ojbd.2012.23008.
 S. Cherian and B. Wood, “Flow Cytometry in Evaluation of Hematopoietic Neoplasms,” CAP Press, Northfield, 2012.
 F. E. Craig and K. A. Foon, “Flow Cytometric Immunophenotyping for Hematologic Neoplasms,” Blood, Vol. 111, No. 8, 2008, pp. 3941-3967.
 The International Agency for Research on Cancer (IARC), “WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue,” 4th Edition, World Health Organization, Lyon, 2008.
 H. E. Johnsen, M. B?gsted, T. W. Klausen, et al., “Multiparametric Flow Cytometry Profiling of Neoplastic Plasma Cells in Multiple Myeloma,” Cytometry Part B: Clinical Cytometry, Vol. 78B, No. 5, 2010, pp. 338-347.
 R. Bataille, G. Jégo, N. Robillard, et al., “The Phenotype of Normal, Reactive and Malignant Plasma Cells. Identification of ‘Many and Multiple Myelomas’ and of New Targets for Myeloma Therapy,” Haematologica, Vol. 91, No. 9, 2006, pp. 1234-1240.
 A. C. Rawstron, A. Orfao, M. Beksac, et al., “Report of the European Myeloma Network on Multiparametric Flow Cytometry in Multiple Myeloma and Related Disorders,” Haematologica, Vol. 93, No. 3, 2008, pp. 431438. doi:10.3324/haematol.11080
 P. Lin, R. Owens, G. Tricot and C. S. Wilson, “Flow Cytometric Immunophenotypic Analysis of 306 Cases of Multiple Myeloma,” American Journal of Clinical Pathology, Vol. 121, No. 4, 2004, pp. 482-488.
 E. Cannizzo, G. Carulli, L. Del Vecchio, et al., “The Role of CD19 and CD27 in the Diagnosis of Multiple Myeloma by Flow Cytometry: A New Statistical Model,” American Journal of Clinical Pathology, Vol. 137, No. 3, 2012, pp. 377-386. doi:10.1309/AJCP63TOCFNAMDMS
 B. Paiva, N. C. Gutiérrez, X. Chen, et al., “Clinical Significance of CD81 Expression by Clonal Plasma Cells in High-Risk Smoldering and Symptomatic Multiple Myeloma Patients,” Leukemia, Vol. 26, No. 8, 2012, pp. 18621869. doi:10.1038/leu.2012.42
 D. Atanackovic, J. Panse, Y. Hildebrandt, et al., “Surface Molecule CD229 as a Novel Target for the Diagnosis and Treatment of Multiple Myeloma,” Haematologica, Vol. 96, No. 10, 2011, pp. 1512-1520.
 C. Lee, B. A. Guinn, S. E. Brooks, D. Richardson and K. Orchard, “CD66a (CEACAM1) Is the Only CD66 Variant Expressed on the Surface of Plasma Cells in Multiple Myeloma: A Refined Target for Radiotherapy Trials?” British Journal of Haematology, Vol. 149, No. 5, 2010, pp. 795-796. doi:10.1111/j.1365-2141.2010.08100.x
 E. Pérez-Persona, M.-B. Vidriales, G. Mateo, et al., “New Criteria to Identify Risk of Progression in Monoclonal Gammopathy of Uncertain Significance and Smoldering Multiple Myeloma Based on Multiparameter Flow Cytometry Analysis of Bone Marrow Plasma Cells,” Blood, Vol. 110, No. 7, 2007, pp. 2586-2592.
 S. V. Rajkumar, G. Gahrton and P. L. Bergsagel, “Approach to the Treatment of Multiple Myeloma: A Clash of Philosophies,” Blood, Vol. 118, No. 12, 2011, pp. 32053211. doi:10.1182/blood-2011-06-297853
 R. Gupta, A. Bhaskar, L. Kumar, A. Sharma and P. Jain, “Flow Cytometric Immunophenotyping and Minimal Residual Disease Analysis in Multiple Myeloma,” American Journal of Clinical Pathology, Vol. 132, No. 5, 2009, pp. 728-732. doi:10.1309/AJCP1GYI7EHQYUYK
 W. Cao, C. L. Goolsby, B. P. Nelson, S. Singhal, J. Mehta and L. C. Peterson, “Instability of Immunophenotype in Plasma Cell Myeloma,” American Journal of Clinical Pathology, Vol. 129, No. 6, 2008, pp. 926-933.
 S. Kumar, S. V. Rajkumar, T. Kimlinger, P. R. Greipp and T. E. Witzig, “CD45 Expression by Bone Marrow Plasma Cells in Multiple Myeloma: Clinical and Biological Correlations,” Leukemia, Vol. 19, No. 8, 2005, pp. 1466-1470. doi:10.1038/sj.leu.2403823
 G. Mateo, M. A. Montalbán, M. B. Vidriales, et al., “Prognostic Value of Immunophenotyping in Multiple Myeloma: A Study by the PETHEMA/GEM Cooperative Study Groups on Patients Uniformly Treated with HighDose Therapy,” Journal of Clinical Oncology, Vol. 26, No. 16, 2008, pp. 2737-2744.
 N.-T. Ngo, C. Brodie, C. Giles, et al., “The Significance of Tumour Cell Immunophenotype in Myeloma and Its Impact on Clinical Outcome,” Journal of Clinical Pathology, Vol. 62, No. 11, 2009, pp. 1009-1015.
 S. A. Ely and D. M. Knowles, “Expression of CD56/ Neural Cell Adhesion Molecule Correlates with the Presence of Lytic Bone Lesions in Multiple Myeloma and Distinguishes Myeloma from Monoclonal Gammopathy of Undetermined Significance and Lymphomas with Plasmacytoid Differentiation,” The American Journal of Pathology, Vol. 160, No. 4, 2002, pp. 1293-1299.
 K. L. M. Boylan, M. A. Gosse, S. E. Staggs, et al., “A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma,” Cancer Research, Vol. 67, No. 9, 2007, pp. 4069-4078.
 W. C. Cheung, J. S. Kim, M. Linden, et al., “Novel Targeted Deregulation of c-Myc Cooperates with Bcl-X(L) to Cause Plasma Cell Neoplasms in Mice,” The Journal of Clinical Investigation,” Vol. 113, No. 12, 2004, pp. 1763-1773.
 M. Linden, N. Kirchhof, C. Carlson and B. Van Ness “Targeted Overexpression of Bcl-XL in B-Lymphoid Cells Results in Lymphoproliferative Disease and Plasma Cell Malignancies,” Blood, Vol. 103, No. 7, 2004, pp. 2779-2786. doi:10.1182/blood-2003-10-3399
 S. Chevrier, C. Genton, A. Kallies, et al., “CD93 Is Required for Maintenance of Antibody Secretion and Persistence of Plasma Cells in the Bone Marrow Niche,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 10, 2009, pp. 3895-3900. doi:10.1073/pnas.0809736106
 G. B. Segel, T. J. Woodlock, J. Xu, et al., “Early Gene Activation in Chronic Leukemic B Lymphocytes Induced toward a Plasma Cell Phenotype,” Blood Cells, Molecules & Diseases, Vol. 30, No. 3, 2003, pp. 277-287.
 B. Rodríguez-Bayona, A. Ramos-Amaya, J. J. PérezVenegas, C. Rodríguez and J. A. Brieva, “Decreased Frequency and Activated Phenotype of Blood CD27 IgD IgM B Lymphocytes Is a Permanent Abnormality in Systemic Lupus Erythematosus Patients,” Arthritis Research & Therapy, Vol. 12, No. 3, 2010, pp. R108-R117.
 S. Hosomi, N. Oshitani, N. Kamata, et al., “Increased Numbers of Immature Plasma Cells in Peripheral Blood Specifically Overexpress Chemokine Receptor CXCR3 and CXCR4 in Patients with Ulcerative Colitis,” Clinical and Experimental Immunology, Vol. 163, No. 2, 2011, pp. 215-224. doi:10.1111/j.1365-2249.2010.04290.x
 A. Caraux, B. Klein, B. Paiva, et al., “Circulating Human B and Plasma Cells. Age-Associated Changes in Counts and Detailed Characterization of Circulating Normal CD138? and CD138+ Plasma Cells,” Haematologica, Vol. 95, No. 6, 2010, pp. 1016-1020.
 M. S. Iqbal, K.-I. Otsuyama, K. Shamsasenjan, et al., “Constitutively Lower Expressions of CD54 on Primary Myeloma Cells and Their Different Localizations in Bone Marrow,” European Journal of Haematology, Vol. 83, No. 4, 2009, pp. 302-312.
 G. Badr, E. A. Lefevre and M. Mohany, “Thymoquinone Inhibits the CXCL12-Induced Chemotaxis of Multiple Myeloma Cells and Increases Their Susceptibility to Fas-Mediated Apoptosis,” PLoS One, Vol. 6, No. 9, 2011, p. e23741. doi:10.1371/journal.pone.0023741
 A. K. Azab, J. M. Runnels, C. Pitsillides, et al., “CXCR4 Inhibitor AMD3100 Disrupts the Interaction of Multiple Myeloma Cells with the Bone Marrow Microenvironment and Enhances Their Sensitivity to Therapy,” Blood, Vol. 113, No. 18, 2009, pp. 4341-4351.
 A. M. Oliveira, D. A. Maria, M. Metzger, et al., “Thalidomide Treatment Down-Regulates SDF-1α and CXCR4 Expression in Multiple Myeloma Patients, Leukemia Research, Vol. 33, No. 7, 2009, pp. 970-973.