Dtsch Med Wochenschr 2016; 141(21): 1569-1574
DOI: 10.1055/s-0042-109432
Fachwissen
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Durchflusszytometrische Immunphänotypisierung in der klinischen Diagnostik

Flow-cytometric immunophenotyping in clinical diagnostics
Benjamin Nils Ostendorf
1   Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
2   Labor Berlin Chariteé Vivantes GmbH, Berlin
3   Laboratory of Systems Cancer Biology, Rockefeller University, New York, USA
,
Leo Hansmann
1   Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
2   Labor Berlin Chariteé Vivantes GmbH, Berlin
,
Wolf-Dieter Ludwig
4   Klinik für Hämatologie, Onkologie, Tumorimmunologie und Palliativmedizin, HELIOS Klinikum Berlin-Buch, Berlin
,
Bernd Dörken
1   Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
2   Labor Berlin Chariteé Vivantes GmbH, Berlin
,
Richard Ratei
4   Klinik für Hämatologie, Onkologie, Tumorimmunologie und Palliativmedizin, HELIOS Klinikum Berlin-Buch, Berlin
,
Jörg Westermann
1   Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin
2   Labor Berlin Chariteé Vivantes GmbH, Berlin
› Author Affiliations
Further Information

Publication History

Publication Date:
17 October 2016 (online)

Zusammenfassung

Die durchflusszytometrische Immunphänotypisierung spielt eine wichtige Rolle in der hämatologisch-immunologischen Routinediagnostik, insbesondere bei der Lymphozytentypisierung sowie der Diagnostik und Verlaufsbeurteilung von benignen und malignen hämatologischen Erkrankungen. Die Möglichkeiten wie auch Limitationen der immunphänotypischen Diagnostik unterliegen einer dynamischen Entwicklung. Die vorliegende Übersichtsarbeit vermittelt einen Überblick über die Indikationsstellung und den gegenwärtigen Stand der durchflusszytometrischen Immunphänotypisierung in der klinischen Routinediagnostik.

Abstract

Flow cytometric immunophenotyping represents an indispensable tool in hematological and immunological diagnostics. The most frequent indications include lymphocyte phenotyping and the diagnosis and monitoring of benign and malignant hematologic diseases. The role of immunophenotyping in clinical practice is evolving rapidly. This review provides an overview of its current applications and limitations.

 
  • Literatur

  • 1 Swerdlow SH, Campo E, Harris NL et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4. Aufl. World Health Organization; Genf: 2008
  • 2 San Miguel JF, Gonzalez M, Cañizo MC et al. Surface marker analysis in acute myeloid leukaemia and correlation with FAB classification. 1986; 64: 547-560
  • 3 Wuchter C, Harbott J, Schoch C et al. Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody. Leukemia 2000; 14: 1232-1238
  • 4 Béné MC, Castoldi G, Knapp W et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).. Leukemia 1995; 9: 1783-1786
  • 5 Basso G, Veltroni M, Valsecchi MG et al. Risk of relapse of childhood acute lymphoblastic leukemia is predicted by flow cytometric measurement of residual disease on day 15 bone marrow. J Clin Oncol 2009; 27: 5168-5174
  • 6 Campana D. Should minimal residual disease monitoring in acute lymphoblastic leukemia be standard of care?. Curr Hematol Malig Rep 2012; 7: 170-177
  • 7 Kern W, Bacher U, Haferlach C et al. The role of multiparameter flow cytometry for disease monitoring in AML. Best Pract Res Clin Haematol 2010; 23: 379-390
  • 8 Gaipa G, Cazzaniga G, Valsecchi MG et al. Time point-dependent concordance of flow cytometry and real-time quantitative polymerase chain reaction for minimal residual disease detection in childhood acute lymphoblastic leukemia. Haematologica 2012; 97: 1582-1593
  • 9 Kern W, Bacher U, Haferlach C et al. Multiparameter flow cytometry provides independent prognostic information in patients with suspected myelodysplastic syndromes: A study on 804 patients. Cytometry B Clin Cytom 2015; 88: 154-164
  • 10 Porta Della MG, Picone C, Pascutto C et al. Multicenter validation of a reproducible flow cytometric score for the diagnosis of low-grade myelodysplastic syndromes: results of a European LeukemiaNET study. Haematologica 2012; 97: 1209-1217
  • 11 Westers TM, Ireland R, Kern W et al. Standardization of flow cytometry in myelodysplastic syndromes: a report from an international consortium and the European LeukemiaNet Working Group. Leukemia 2012; 26: 1730-1741
  • 12 Escribano L, Díaz-Agustín B, Bellas C et al. Utility of flow cytometric analysis of mast cells in the diagnosis and classification of adult mastocytosis. Leukemia Res 2001; 25: 563-570
  • 13 Pozdnyakova O, Kondtratiev S, Li B et al. High-sensitivity flow cytometric analysis for the evaluation of systemic mastocytosis including the identification of a new flow cytometric criterion for bone marrow involvement. Am J Clin Pathol 2012; 138: 416-424
  • 14 Colorado M, Cuadrado MA, Insunza A et al. Simultaneous cytomorphologic and multiparametric flow cytometric analysis on lymph node samples is faster than and as valid as histopathologic study to diagnose most Non-Hodgkin Lymphomas. Am J Clin pathol 2010; 133: 83-91
  • 15 Craig FE, Foon KA. Flow cytometric immunophenotyping for hematologic neoplasms. Blood 2008; 111: 3941-3967
  • 16 Böttcher S, Ritgen M, Kneba M. Flow cytometric MRD detection in selected mature B-cell malignancies. Methods Mol Biol 2013; 97: 149-174
  • 17 Crespo M, Bosch F, Villamor N et al. ZAP-70 expression as a surrogate for immunoglobulinvariable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348: 1764-1775
  • 18 Damle RN, Wasil T, Fais F et al. Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 1999; 94: 1840-1847
  • 19 Hallek M, Cheson BD, Catovsky D et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446-5456
  • 20 Rawstron AC, Orfao A, Beksac M et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008; 93: 431-438
  • 21 Weisberger J, Cornfield D, Gorczyca W et al. Down-regulation of pan-T-cell antigens, particularly CD7, in acute infectious mononucleosis. American Journal of Clinical Pathology 2003; 120: 49-55
  • 22 Beck RC, Stahl S, O’Keefe CL et al. Detection of mature T-Cell leukemias by flow cytometry using anti–T-cell receptor Vβ antibodies. Am J Clin Pathol 2003; 120: 785-794
  • 23 Langerak AW, Szczepański T, van der Burg M et al. Heteroduplex PCR analysis of rearranged T cell receptor genes for clonality assessment in suspect T cell proliferations. 1997; 11: 2192-2199
  • 24 Parker C. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood 2005; 106: 3699-3709
  • 25 Sutherland DR, Keeney M, Illingworth A. Practical guidelines for the high-sensitivity detection and monitoring of paroxysmal nocturnal hemoglobinuria clones by flow cytometry. Cytometry B Clin Cytom 2012; 82: 195-208
  • 26 King MJ, Smythe JS, Mushens R. Eosin-5-maleimide binding to band 3 and Rh-related proteins forms the basis of a screening test for hereditary spherocytosis. Br J Haematol 2004; 124: 106-113
  • 27 Maartens G, Celum C, Lewin SR. HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 2014; 384: 258-271
  • 28 de Vries E, Noordzij JG, Kuijpers TW et al. Flow cytometric immunophenotyping in the diagnosis and follow-up of immunodeficient children. Eur J Pediatr 2001; 160: 583-591
  • 29 Oliveira JB, Notarangelo LD, Fleisher TA. Applications of flow cytometry for the study of primary immune deficiencies. Curr Opin Allergy Clin Immunol 2008; 8: 499-509
  • 30 Linden MD, Frelinger AL, Barnard MR et al. Application of flow cytometry to platelet disorders. Semin. Thromb Hemost 2004; 30: 501-511
  • 31 Carulli G. Applications of flow cytometry in the study of human neutrophil biology and pathology. Hematopathol Mol Hematol 1996; 10: 39-61
  • 32 Gratama JW, Sutherland DR, Keeney M. Flow cytometric enumeration and immunophenotyping of hematopoietic stem and progenitor cells. Semin Hematol 2001; 38: 139-147
  • 33 Davis BH, Dasgupta A, Kussick S et al. Validation of cell-based fluorescence assays: practice guidelines from the ICSH and ICCS – part II – preanalytical issues. Cytometry B Clin Cytom 2013; 84: 286-290
  • 34 Ng AAP, Lee BTK, Teo TSY et al. Optimal cellular preservation for high dimensional flow cytometric analysis of multicentre trials. J Immunol Meth 2012; 385: 79-89
  • 35 Dux R, Kindler-Röhrborn A, Annas M et al. A standardized protocol for flow cytometric analysis of cells isolated from cerebrospinal fluid. J Neurol Sci 1994; 121: 74-78
  • 36 Jongste AH, Kraan J, van den Broek PD et al. Use of TransFix™ cerebrospinal fluid storage tubes prevents cellular loss and enhances flow cytometric detection of malignant hematological cells after 18 hours of storage. Cytometry B Clin Cytom 2014; 86: 272-279
  • 37 Chattopadhyay PK, Roederer M. A mine is a terrible thing to waste: high content, single cell technologies for comprehensive immune analysis. Am J Transplant 2015; 15: 1155-1161
  • 38 Kling J. Cytometry: Measure for measure. Nature 2015; 518: 439-443
  • 39 Spitzer MH, Gherardini PF, Fragiadakis GK et al. IMMUNOLOGY. An interactive reference framework for modeling a dynamic immune system. Science 2015; 349: 1259425-1259425
  • 40 Hansmann L, Blum L, Ju CH et al. Mass cytometry analysis shows that a novel memory phenotype B cell is expanded in multiple myeloma. Cancer Immunol Res 2015; 3: 650-660