title: Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma.
abstract: In recent years, several studies on large series of multiple myeloma (MM) patients have demonstrated the clinical utility of flow cytometry monitoring of minimal residual disease (flow-MRD) in bone marrow (BM), for improved assessment of response to therapy and prognostication. However, disturbing levels of variability exist regarding the specific protocols and antibody panels used in individual laboratories. Overall, consensus exists about the utility of combined assessment of CD38 and CD138 for the identification of BM plasma cells (PC); in contrast, more heterogeneous lists of markers are used to further distinguish between normal/reactive PCs and myeloma PCs in the MRD settings. Among the later markers, CD19, CD45, CD27, and CD81, together with CD56, CD117, CD200, and CD307, have emerged as particularly informative; however, no single marker provides enough specificity for clear discrimination between clonal PCs and normal PCs. Accordingly, multivariate analyses of single PCs from large series of normal/reactive vs. myeloma BM samples have shown that combined assessment of CD138 and CD38, together with CD45, CD19, CD56, CD27, CD81, and CD117 would be ideally suited for MRD monitoring in virtually every MM patient. However, the specific antibody clones, fluorochrome conjugates and sources of the individual markers determines its optimal (vs. suboptimal or poor) performance in an eight-color staining. Assessment of clonality, via additional cytoplasmic immunoglobulin (CyIg) κ vs. CyIgλ evaluation, may contribute to further establish the normal/reactive vs. clonal nature of small suspicious PC populations at high sensitivity levels, provided that enough cells are evaluated.
authors.affiliation: Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Flores-Montero
authors.affiliation: Haematological Malignancy Diagnostic Service, St James Institute of Oncology, Leeds Teaching Hospitals, Leeds, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: de Tute
authors.affiliation: Clínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.
authors.forename: Bruno
authors.initials: B
authors.lastname: Paiva
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.
authors.forename: José Juan
authors.initials: JJ
authors.lastname: Perez
authors.affiliation: Second Department of Medicine, University Hospital of Schleswig Holstein, Campus Kiel (UNIKIEL), Kiel, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Böttcher
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Wind
authors.affiliation: Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.
authors.forename: Luzalba
authors.initials: L
authors.lastname: Sanoja
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Puig
authors.affiliation: Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Lecrevisse
authors.affiliation: Department of Hematology, Hospital Universitario de Salamanca, Instituto Biosanitario de Salamanca (IBSAL), Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Salamanca, Spain.
authors.forename: María Belén
authors.initials: MB
authors.lastname: Vidriales
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam (Erasmus MC), Rotterdam, The Netherlands.
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.affiliation: Centro de Investigación del Cáncer (Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL), Instituto Biosanitario de Salamanca (IBSAL), Servicio de Citometría y Departamento de Medicina-NUCLEUS, Universidad de Salamanca (Salamanca), Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
mesh_terms: D000906:Antibodies / Q000737:chemistry* / Q000145:classification; D015703:Antigens, CD / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002999:Clone Cells; D005434:Flow Cytometry / Q000592:standards*; D015870:Gene Expression; D006801:Humans; D016130:Immunophenotyping / Q000592:standards*; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D011379:Prognosis; D012074:Remission Induction; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000970:Antineoplastic Agents
keywords: EuroFlow; antibody panels; high sensitivity; markers; minimal residual disease; multiple myeloma