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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter / Tate, Jillian R.

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Volume 44, Issue 7 (Jul 2006)

Issues

Flow-cytometric immunophenotyping of normal and malignant lymphocytes

Tomasz Szczepański
  • Department of Immunology, Erasmus MC, Rotterdam, The Netherlands and Department of Pediatric Hematology and Oncology, Silesian Medical Academy, Zabrze, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Vincent H.J. van der Velden / Jacques J.M. van Dongen
Published Online: 2006-06-16 | DOI: https://doi.org/10.1515/CCLM.2006.146

Abstract

During the past two decades, flow-cytometric immunophenotyping of lymphocytes has evolved from a research technique into a routine laboratory diagnostic test. Extensive studies in healthy individuals resulted in detailed age-related reference values for different lymphocyte subpopulations in peripheral blood. This is an important tool for the diagnosis of hematological and immunological disorders. Similar, albeit less detailed, information is now available for other lymphoid organs, e.g., normal bone marrow, lymph nodes, tonsils, thymus and spleen. Flow-cytometric immunophenotyping forms the basis of modern classification of acute and chronic leukemias and is increasingly applied for initial diagnostic work-up of non-Hodgkin's lymphomas. Finally, with multiparameter flow cytometry, it is now possible to identify routinely and reliably low numbers of leukemia and lymphoma cells (minimal residual disease).

Clin Chem Lab Med 2006;44:775–96.

Keywords: bone marrow; CD markers; flow cytometry; leukemias; lymph node; lymphocyte; lymphomas; minimal residual disease; peripheral blood

References

  • 1.

    Jennings CD, Foon KA. Recent advances in flow cytometry: application to the diagnosis of hematologic malignancy. Blood 1997; 90:2863–92.Google Scholar

  • 2.

    Basso G, Buldini B, De Zen L, Orfao A. New methodologic approaches for immunophenotyping acute leukemias. Haematologica 2001; 86:675–92.Google Scholar

  • 3.

    Bain BJ, Barnett D, Linch D, Matutes E, Reilly JT. Revised guideline on immunophenotyping in acute leukaemias and chronic lymphoproliferative disorders. Clin Lab Haematol 2002; 24:1–13.CrossrefGoogle Scholar

  • 4.

    Weir EG, Cowan K, LeBeau P, Borowitz MJ. A limited antibody panel can distinguish B-precursor acute lymphoblastic leukemia from normal B precursors with four color flow cytometry: implications for residual disease detection. Leukemia 1999; 13:558–67.CrossrefGoogle Scholar

  • 5.

    Bigos M, Baumgarth N, Jager GC, Herman OC, Nozaki T, Stovel RT, et al. Nine-color eleven-parameter immunophenotyping using three laser flow cytometry. Cytometry 1999; 36:36–45.CrossrefGoogle Scholar

  • 6.

    Shah VO, Civin CI, Loken MR. Flow cytometric analysis of human bone marrow. IV. Differential quantitative expression of T-200 common leukocyte antigen during normal hemopoiesis. J Immunol 1988; 140:1861–7.Google Scholar

  • 7.

    van Dongen JJ, Szczepański T, Adriaansen HJ. Immunobiology of leukemia. In: Henderson ES, Lister TA, Greaves MF, editors. Leukemia. Philadelphia, PA: WB Saunders, 2002:85–129.Google Scholar

  • 8.

    Mason D, Andre P, Bensussan A, Buckley C, Civin C, Clark E, et al. Reference: CD Antigens 2002. J Immunol 2002; 168:2083–6.CrossrefGoogle Scholar

  • 9.

    Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, et al. CD molecules 2005: human cell differentiation molecules. Blood 2005; 106:3123–6.CrossrefGoogle Scholar

  • 10.

    Escribano L, Ocqueteau M, Almeida J, Orfao A, San Miguel JF. Expression of the c-kit (CD117) molecule in normal and malignant hematopoiesis. Leuk Lymphoma 1998; 30:459–66.Google Scholar

  • 11.

    Adriaansen HJ, Hooijkaas H, Kappers-Klunne MC, Hahlen K, van't Veer MB, van Dongen JJ. Double marker analysis for terminal deoxynucleotidyl transferase and myeloid antigens in acute nonlymphocytic leukemia patients and healthy subjects. Haematol Blood Transfus 1990; 33:41–9.Google Scholar

  • 12.

    Blair A, Hogge DE, Ailles LE, Lansdorp PM, Sutherland HJ. Lack of expression of Thy-1 (CD90) on acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo. Blood 1997; 89:3104–12.Google Scholar

  • 13.

    Baersch G, Baumann M, Ritter J, Jurgens H, Vormoor J. Expression of AC133 and CD117 on candidate normal stem cell populations in childhood B-cell precursor acute lymphoblastic leukaemia. Br J Haematol 1999; 107:572–80.Google Scholar

  • 14.

    Craig W, Kay R, Cutler RL, Lansdorp PM. Expression of Thy-1 on human hematopoietic progenitor cells. J Exp Med 1993; 177:1331–42.Google Scholar

  • 15.

    Yin AH, Miraglia S, Zanjani ED, Almeida-Porada G, Ogawa M, Leary AG, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997; 90:5002–12.Google Scholar

  • 16.

    Foon KA, Todd RF. Immunologic classification of leukemia and lymphoma. Blood 1986; 68:1–31.Google Scholar

  • 17.

    van Dongen JJ, Adriaansen HJ, Hooijkaas H. Immunophenotyping of leukaemias and non-Hodgkin's lymphomas. Immunological markers and their CD codes. Neth J Med 1988; 33:298–314.Google Scholar

  • 18.

    Borst J, Brouns GS, de Vries E, Verschuren MC, Mason DY, van Dongen JJ. Antigen receptors on T and B lymphocytes: parallels in organization and function. Immunol Rev 1993; 132:49–84.CrossrefGoogle Scholar

  • 19.

    Dworzak MN, Fritsch G, Froschl G, Printz D, Gadner H. Four-color flow cytometric investigation of terminal deoxynucleotidyl transferase-positive lymphoid precursors in pediatric bone marrow: CD79a expression precedes CD19 in early B-cell ontogeny. Blood 1998; 92:3203–9.Google Scholar

  • 20.

    Noordzij JG, de Bruin-Versteeg S, Comans-Bitter WM, Hartwig NG, Hendriks RW, de Groot R, et al. Composition of precursor B-cell compartment in bone marrow from patients with X-linked agammaglobulinemia compared with healthy children. Pediatr Res 2002; 51:159–68.CrossrefGoogle Scholar

  • 21.

    Tsuganezawa K, Kiyokawa N, Matsuo Y, Kitamura F, Toyama-Sorimachi N, Kuida K, et al. Flow cytometric diagnosis of the cell lineage and developmental stage of acute lymphoblastic leukemia by novel monoclonal antibodies specific to human pre-B-cell receptor. Blood 1998; 92:4317–24.Google Scholar

  • 22.

    van Dongen JJ, Krissansen GW, Wolvers-Tettero IL, Comans-Bitter WM, Adriaansen HJ, Hooijkaas H, et al. Cytoplasmic expression of the CD3 antigen as a diagnostic marker for immature T-cell malignancies. Blood 1988; 71:603–12.Google Scholar

  • 23.

    van Dongen JJ, Comans-Bitter WM, Wolvers-Tettero IL, Borst J. Development of human T lymphocytes and their thymus dependency. Thymus 1990; 16:207–34.Google Scholar

  • 24.

    Castrop J, van Wichen D, Comans-Bitter WM, van de Wetering M, de Weger R, van Dongen JJ, et al. The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes. Blood 1995; 86:3050–9.Google Scholar

  • 25.

    van den Beemd MW, Boor PP, Van Lochem EG, Hop WC, Langerak AW, Wolvers-Tettero IL, et al. Flow cytometric analysis of the Vβ repertoire in healthy controls. Cytometry 2000; 40:336–45.CrossrefGoogle Scholar

  • 26.

    Lanier LL, Le AM, Civin CI, Loken MR, Phillips JH. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 1986; 136:4480–6.Google Scholar

  • 27.

    Moretta L, Moretta A. Unravelling natural killer cell function: triggering and inhibitory human NK receptors. EMBO J 2004; 23:255–9.CrossrefGoogle Scholar

  • 28.

    Moretta A, Biassoni R, Bottino C, Mingari MC, Moretta L. Natural cytotoxicity receptors that trigger human NK-cell-mediated cytolysis. Immunol Today 2000; 21:228–34.CrossrefGoogle Scholar

  • 29.

    Moretta L, Moretta A. Killer immunoglobulin-like receptors. Curr Opin Immunol 2004; 16:626–33.CrossrefGoogle Scholar

  • 30.

    Bisset LR, Lung TL, Kaelin M, Ludwig E, Dubs RW. Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland. Eur J Haematol 2004; 72:203–12.CrossrefGoogle Scholar

  • 31.

    Comans-Bitter WM, de Groot R, van den Beemd R, Neijens HJ, Hop WC, Groeneveld K, et al. Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr 1997; 130:388–93.CrossrefGoogle Scholar

  • 32.

    Shearer WT, Rosenblatt HM, Gelman RS, Oyomopito R, Plaeger S, Stiehm ER, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol 2003; 112:973–80.CrossrefGoogle Scholar

  • 33.

    Youinou P, Jamin C, Lydyard PM. CD5 expression in human B-cell populations. Immunol Today 1999; 20:312–6.Google Scholar

  • 34.

    Agematsu K, Hokibara S, Nagumo H, Komiyama A. CD27: a memory B-cell marker. Immunol Today 2000; 21:204–6.CrossrefGoogle Scholar

  • 35.

    Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA. CD4+ CD25 high regulatory cells in human peripheral blood. J Immunol 2001; 167:1245–53.Google Scholar

  • 36.

    Fehervari Z, Sakaguchi S. CD4+ Tregs and immune control. J Clin Invest 2004; 114:1209–17.CrossrefGoogle Scholar

  • 37.

    Ho LP, Urban BC, Thickett DR, Davies RJ, McMichael AJ. Deficiency of a subset of T-cells with immunoregulatory properties in sarcoidosis. Lancet 2005; 365:1062–72.CrossrefGoogle Scholar

  • 38.

    Kronenberg M, Rudensky A. Regulation of immunity by self-reactive T cells. Nature 2005; 435:598–604.CrossrefGoogle Scholar

  • 39.

    Lima M, Almeida J, dos Anjos Teixeira M, Queiros ML, Justica B, Orfao A. The “ex vivo” patterns of CD2/CD7, CD57/CD11c, CD38/CD11b, CD45RA/CD45RO, and CD11a/HLA-DR expression identify acute/early and chronic/late NK-cell activation states. Blood Cells Mol Dis 2002; 28:181–90.CrossrefGoogle Scholar

  • 40.

    Rego EM, Garcia AB, Viana SR, Falcao RP. Age-related changes of lymphocyte subsets in normal bone marrow biopsies. Cytometry 1998; 34:22–9.CrossrefGoogle Scholar

  • 41.

    van Lochem EG, van der Velden VH, Wind HK, te Marvelde JG, Westerdaal NA, van Dongen JJ. Immunophenotypic differentiation patterns of normal hematopoiesis in human bone marrow: reference patterns for age-related changes and disease-induced shifts. Cytometry 2004; 60B:1–13.CrossrefGoogle Scholar

  • 42.

    Battaglia A, Ferrandina G, Buzzonetti A, Malinconico P, Legge F, Salutari V, et al. Lymphocyte populations in human lymph nodes. Alterations in CD4+CD25+ T regulatory cell phenotype and T-cell receptor Vβ repertoire. Immunology 2003; 110:304–12.CrossrefGoogle Scholar

  • 43.

    Almasri NM, Iturraspe JA, Braylan RC. CD10 expression in follicular lymphoma and large cell lymphoma is different from that of reactive lymph node follicles. Arch Pathol Lab Med 1998; 122:539–44.Google Scholar

  • 44.

    Bergler W, Adam S, Gross HJ, Hormann K, Schwartz-Albiez R. Age-dependent altered proportions in sub-populations of tonsillar lymphocytes. Clin Exp Immunol 1999; 116:9–18.CrossrefGoogle Scholar

  • 45.

    Colovai AI, Giatzikis C, Ho EK, Farooqi M, Suciu-Foca N, Cattoretti G, et al. Flow cytometric analysis of normal and reactive spleen. Mod Pathol 2004; 17:918–27.CrossrefGoogle Scholar

  • 46.

    Weerkamp F, de Haas EF, Naber BA, Comans-Bitter WM, Bogers AJ, van Dongen JJ, et al. Age-related changes in the cellular composition of the thymus in children. J Allergy Clin Immunol 2005; 115:834–40.CrossrefGoogle Scholar

  • 47.

    Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, et al. The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting – Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17:3835–49.CrossrefGoogle Scholar

  • 48.

    Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. Lyon: IARC Press, 2001:352pp.Google Scholar

  • 49.

    van Wering ER, van Lochem EG, Leenders M, van der Sluijs-Gelling AJ, Wind H, Gratama JW, et al. Three-color flow cytometric analysis of mature and immature hematological malignancies. A guideline of the Dutch Foundation for Immunophenotyping of Hematological Malignancies (SIHON). J Biol Regul Homeost Agents 2004; 18:313–26.Google Scholar

  • 50.

    Basso G, Bernasconi P, Chianese R, Crovetti G, Garbaccio G, Iavarone A, et al. Monoclonal antibody panels for acute leukemia and myelodysplastic syndrome diagnosis. Results of a co-operative quality control group. J Biol Regul Homeost Agents 2001; 15:145–55.Google Scholar

  • 51.

    Borowitz MJ, Bray R, Gascoyne R, Melnick S, Parker JW, Picker L, et al. US-Canadian Consensus recommendations on the immunophenotypic analysis of hematologic neoplasia by flow cytometry: data analysis and interpretation. Cytometry 1997; 30:236–44.CrossrefGoogle Scholar

  • 52.

    Ratei R, Karawajew L, Lacombe F, Jagoda K, Del Poeta G, Kraan J, et al. Normal lymphocytes from leukemic samples as an internal quality control for fluorescence intensity in immunophenotyping of acute leukemias. Cytometry B 2006; 70:1–9.CrossrefGoogle Scholar

  • 53.

    Szczepański T, van der Velden VH, van Dongen JJ. Classification systems for acute and chronic leukaemias. Best Pract Res Clin Haematol 2003; 16:561–82.CrossrefGoogle Scholar

  • 54.

    Bene MC, Castoldi G, Knapp W, Ludwig WD, Matutes E, Orfao A, et al. Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia 1995; 9:1783–6.Google Scholar

  • 55.

    van der Burg M, Barendregt BH, van Wering ER, Langerak AW, Szczepański T, van Dongen JJ. The presence of somatic mutations in immunoglobulin genes of B-cell acute lymphoblastic leukemia (ALL-L3) supports assignment as Burkitt's leukemia-lymphoma rather than B-lineage ALL. Leukemia 2001; 15:1141–3.CrossrefGoogle Scholar

  • 56.

    Hrusak O, Porwit-MacDonald A. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia 2002; 16:1233–58.CrossrefGoogle Scholar

  • 57.

    Borkhardt A, Wuchter C, Viehmann S, Pils S, Teigler-Schlegel A, Stanulla M, et al. Infant acute lymphoblastic leukemia – combined cytogenetic, immunophenotypical and molecular analysis of 77 cases. Leukemia 2002; 16:1685–90.CrossrefGoogle Scholar

  • 58.

    Behm FG, Smith FO, Raimondi SC, Pui CH, Bernstein ID. Human homologue of the rat chondroitin sulfate proteoglycan, NG2, detected by monoclonal antibody 7.1, identifies childhood acute lymphoblastic leukemias with t(4;11)(q21;q23) or t(11;19)(q23;p13) and MLL gene rearrangements. Blood 1996; 87:1134–9.Google Scholar

  • 59.

    De Zen L, Bicciato S, te Kronnie G, Basso G. Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification. Leukemia 2003; 17:1557–65.Google Scholar

  • 60.

    Borowitz MJ, Hunger SP, Carroll AJ, Shuster JJ, Pullen DJ, Steuber CP, et al. Predictability of the t(1;19)p13) from surface antigen phenotype: implications for screening cases of childhood acute lymphoblastic leukemia for molecular analysis: a Pediatric Oncology Group study. Blood 1993; 82:1086–91.Google Scholar

  • 61.

    De Zen L, Orfao A, Cazzaniga G, Masiero L, Cocito MG, Spinelli M, et al. Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification. Leukemia 2000; 14:1225–31.Google Scholar

  • 62.

    Mori T, Sugita K, Suzuki T, Okazaki T, Manabe A, Hosoya R, et al. A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity. Leukemia 1995; 9:1233–9.Google Scholar

  • 63.

    Paietta E, Racevskis J, Neuberg D, Rowe JM, Goldstone AH, Wiernik PH. Expression of CD25 (interleukin-2 receptor alpha chain) in adult acute lymphoblastic leukemia predicts for the presence of BCR/ABL fusion transcripts: results of a preliminary laboratory analysis of ECOG/MRC Intergroup Study E2993. Eastern Cooperative Oncology Group/Medical Research Council. Leukemia 1997; 11:1887–90.Google Scholar

  • 64.

    Asnafi V, Beldjord K, Boulanger E, Comba B, Le Tutour P, Estienne MH, et al. Analysis of TCR, pT alpha, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood 2003; 101:2693–703.CrossrefGoogle Scholar

  • 65.

    Langerak AW, Wolvers-Tettero IL, van den Beemd MW, van Wering ER, Ludwig W-D, Hählen K, et al. Immunophenotypic and immunogenotypic characteristics of TCRgd+ T cell acute lymphoblastic leukemia. Leukemia 1999; 13:206–14.CrossrefGoogle Scholar

  • 66.

    Geisler CH, Larsen JK, Hansen NE, Hansen MM, Christensen BE, Lund B, et al. Prognostic importance of flow cytometric immunophenotyping of 540 consecutive patients with B-cell chronic lymphocytic leukemia. Blood 1991; 78:1795–802.Google Scholar

  • 67.

    Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 1999; 94:1848–54.Google Scholar

  • 68.

    Crespo M, Bosch F, Villamor N, Bellosillo B, Colomer D, Rozman M, et al. ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003; 348:1764–75.CrossrefGoogle Scholar

  • 69.

    Matutes E, Owusu-Ankomah K, Morilla R, Garcia Marco J, Houlihan A, Que TH, et al. The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia 1994; 8:1640–5.Google Scholar

  • 70.

    Robbins BA, Ellison DJ, Spinosa JC, Carey CA, Lukes RJ, Poppema S, et al. Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia. Blood 1993; 82:1277–87.Google Scholar

  • 71.

    Stetler-Stevenson M. Flow cytometry in lymphoma diagnosis and prognosis: useful? Best Pract Res Clin Haematol 2003; 16:583–97.CrossrefGoogle Scholar

  • 72.

    Dunphy CH. Contribution of flow cytometric immunophenotyping to the evaluation of tissues with suspected lymphoma? Cytometry 2000; 42:296–306.CrossrefGoogle Scholar

  • 73.

    Laane E, Tani E, Bjorklund E, Elmberger G, Everaus H, Skoog L, et al. Flow cytometric immunophenotyping including Bcl-2 detection on fine needle aspirates in the diagnosis of reactive lymphadenopathy and non-Hodgkin's lymphoma. Cytometry B Clin Cytom 2005; 64:34–42.Google Scholar

  • 74.

    Argatoff LH, Connors JM, Klasa RJ, Horsman DE, Gascoyne RD. Mantle cell lymphoma: a clinicopathologic study of 80 cases. Blood 1997; 89:2067–78.Google Scholar

  • 75.

    Tbakhi A, Edinger M, Myles J, Pohlman B, Tubbs RR. Flow cytometric immunophenotyping of non-Hodgkin's lymphomas and related disorders. Cytometry 1996; 25:113–24.CrossrefGoogle Scholar

  • 76.

    De Leval L, Harris NL. Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance. Histopathology 2003; 43:509–28.CrossrefGoogle Scholar

  • 77.

    Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, et al. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood 1998; 92:3152–62.Google Scholar

  • 78.

    Akasaka T, Akasaka H, Ueda C, Yonetani N, Maesako Y, Shimizu A, et al. Molecular and clinical features of non-Burkitt's, diffuse large-cell lymphoma of B-cell type associated with the c-MYC/immunoglobulin heavy-chain fusion gene. J Clin Oncol 2000; 18:510–8.CrossrefGoogle Scholar

  • 79.

    Matutes E, Morilla R, Owusu-Ankomah K, Houlihan A, Catovsky D. The immunophenotype of splenic lymphoma with villous lymphocytes and its relevance to the differential diagnosis with other B-cell disorders. Blood 1994; 83:1558–62.Google Scholar

  • 80.

    San Miguel JF, Vidriales MB, Ocio E, Mateo G, Sanchez-Guijo F, Sanchez ML, et al. Immunophenotypic analysis of Waldenstrom's macroglobulinemia. Semin Oncol 2003; 30:187–95.CrossrefGoogle Scholar

  • 81.

    Almeida J, Orfao A, Ocqueteau M, Mateo G, Corral M, Caballero MD, et al. High-sensitive immunophenotyping and DNA ploidy studies for the investigation of minimal residual disease in multiple myeloma. Br J Haematol 1999; 107:121–31.CrossrefGoogle Scholar

  • 82.

    Rawstron AC, Davies FE, DasGupta R, Ashcroft AJ, Patmore R, Drayson MT, et al. Flow cytometric disease monitoring in multiple myeloma: the relationship between normal and neoplastic plasma cells predicts outcome after transplantation. Blood 2002; 100:3095–100.CrossrefGoogle Scholar

  • 83.

    Brinkman K, van Dongen JJ, van Lom K, Groeneveld K, Misere JF, van der Heul C. Induction of clinical remission in T-large granular lymphocyte leukemia with cyclosporin A, monitored by use of immunophenotyping with Vβ antibodies. Leukemia 1998; 12:150–4.CrossrefGoogle Scholar

  • 84.

    Langerak AW, van Den Beemd R, Wolvers-Tettero IL, Boor PP, van Lochem EG, Hooijkaas H, et al. Molecular and flow cytometric analysis of the Vβ repertoire for clonality assessment in mature TCRαβ T-cell proliferations. Blood 2001; 98:165–73.CrossrefGoogle Scholar

  • 85.

    Langerak AW, Szczepański T, van der Burg M, Wolvers-Tettero IL, van Dongen JJ. Heteroduplex PCR analysis of rearranged T cell receptor genes for clonality assessment in suspect T cell proliferations. Leukemia 1997; 11:2192–9.CrossrefGoogle Scholar

  • 86.

    van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003; 17:2257–317.Google Scholar

  • 87.

    Haedicke W, Ho FC, Chott A, Moretta L, Rüdiger T, Ott G, et al. Expression of CD94/NKG2A and killer immunoglobulin-like receptors in NK cells and a subset of extranodal cytotoxic T-cell lymphomas. Blood 2000; 95:3628–30.Google Scholar

  • 88.

    Morice WG, Kurtin PJ, Leibson PJ, Tefferi A, Hanson CA. Demonstration of aberrant T-cell and natural killer-cell antigen expression in all cases of granular lymphocytic leukaemia. Br J Haematol 2003; 120:1026–36.CrossrefGoogle Scholar

  • 89.

    Zambello R, Falco M, Della Chiesa M, Trentin L, Carollo D, Castriconi R, et al. Expression and function of KIR and natural cytotoxicity receptors in NK-type lymphoproliferative diseases of granular lymphocytes (LDGL). Blood 2003; 102:1797–805.CrossrefGoogle Scholar

  • 90.

    Matutes E, Brito-Babapulle V, Swansbury J, Ellis J, Morilla R, Dearden C, et al. Clinical and laboratory features of 78 cases of T-prolymphocytic leukemia. Blood 1991; 78:3269–74.Google Scholar

  • 91.

    Willemze R, Kerl H, Sterry W, Berti E, Cerroni L, Chimenti S, et al. EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer. Blood 1997; 90:354–71.Google Scholar

  • 92.

    Greer JP, Kinney MC, Loughran TP Jr. T cell and NK cell lymphoproliferative disorders. Hematology (Am Soc Hematol Educ Program) 2001;259–81.Google Scholar

  • 93.

    Semenzato G, Zambello R, Starkebaum G, Oshimi K, Loughran TP Jr. The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 1997; 89:256–60.Google Scholar

  • 94.

    Zambello R, Semenzato G. Large granular lymphocytosis. Haematologica 1998; 83:936–42.Google Scholar

  • 95.

    Ahmad E, Kingma DW, Jaffe ES, Schrager JA, Janik J, Wilson W, et al. Flow cytometric immunophenotypic profiles of mature gamma delta T-cell malignancies involving peripheral blood and bone marrow. Cytometry B Clin Cytom 2005; 67:6–12.CrossrefGoogle Scholar

  • 96.

    Sandberg Y, Almeida J, Gonzalez M, Lima M, Szczepański T, van Gastel-Mol EJ, et al. Clonal TCRgd+ large granular lymphocyte proliferations reflect the spectrum of normal TCRgd+ T-cells in peripheral blood. Leukemia 2006. In press.Google Scholar

  • 97.

    Breit TM, Wolvers-Tettero IL, van Dongen JJ. Unique selection determinant in polyclonal V delta 2-J delta 1 junctional regions of human peripheral gamma delta T lymphocytes. J Immunol 1994; 152:2860–4.Google Scholar

  • 98.

    Mori KL, Egashira M, Oshimi K. Differentiation stage of natural killer cell-lineage lymphoproliferative disorders based on phenotypic analysis. Br J Haematol 2001; 115:225–8.CrossrefGoogle Scholar

  • 99.

    Cooke CB, Krenacs L, Stetler-Stevenson M, Greiner TC, Raffeld M, Kingma DW, et al. Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin. Blood 1996; 88:4265–74.Google Scholar

  • 100.

    Szczepański T, Orfao A, van der Velden VH, San Miguel JF, van Dongen JJ. Minimal residual disease in leukaemia patients. Lancet Oncol 2001; 2:409–17.CrossrefGoogle Scholar

  • 101.

    Campana D, Coustan-Smith E. Detection of minimal residual disease in acute leukemia by flow cytometry. Cytometry 1999; 38:139–52.CrossrefGoogle Scholar

  • 102.

    van der Velden VH, Hochhaus A, Cazzaniga G, Szczepański T, Gabert J, van Dongen JJ. Detection of minimal residual disease in hematologic malignancies by real-time quantitative PCR: principles, approaches, and laboratory aspects. Leukemia 2003; 17:1013–34.CrossrefGoogle Scholar

  • 103.

    Gabert J, Beillard E, van der Velden VH, Bi W, Grimwade D, Pallisgaard N, et al. Standardization and quality control studies of “real-time” quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. Leukemia 2003; 17:2318–57.CrossrefGoogle Scholar

  • 104.

    Coustan-Smith E, Behm FG, Sanchez J, Boyett JM, Hancock ML, Raimondi SC, et al. Immunological detection of minimal residual disease in children with acute lymphoblastic leukaemia. Lancet 1998; 351:550–4.CrossrefGoogle Scholar

  • 105.

    van Dongen JJ, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, et al. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 1998; 352:1731–8.CrossrefGoogle Scholar

  • 106.

    Coustan-Smith E, Gajjar A, Hijiya N, Razzouk BI, Ribeiro RC, Rivera GK, et al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia after first relapse. Leukemia 2004; 18:499–504.CrossrefGoogle Scholar

  • 107.

    Dworzak MN, Froschl G, Printz D, Mann G, Potschger U, Muhlegger N, et al. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002; 99:1952–8.CrossrefGoogle Scholar

  • 108.

    Bjorklund E, Mazur J, Soderhall S, Porwit-MacDonald A. Flow cytometric follow-up of minimal residual disease in bone marrow gives prognostic information in children with acute lymphoblastic leukemia. Leukemia 2003; 17:138–48.CrossrefGoogle Scholar

  • 109.

    Vidriales MB, Perez JJ, Lopez-Berges MC, Gutierrez N, Ciudad J, Lucio P, et al. Minimal residual disease in adolescent (older than 14 years) and adult acute lymphoblastic leukemias: early immunophenotypic evaluation has high clinical value. Blood 2003; 101:4695–700.CrossrefGoogle Scholar

  • 110.

    Corradini P, Ladetto M, Pileri A, Tarella C. Clinical relevance of minimal residual disease monitoring in non-Hodgkin's lymphomas: a critical reappraisal of molecular strategies. Leukemia 1999; 13:1691–5.CrossrefGoogle Scholar

  • 111.

    Bottcher S, Ritgen M, Pott C, Bruggemann M, Raff T, Stilgenbauer S, et al. Comparative analysis of minimal residual disease detection using four-color flow cytometry, consensus IgH-PCR, and quantitative IgH PCR in CLL after allogeneic and autologous stem cell transplantation. Leukemia 2004; 18:1637–45.CrossrefGoogle Scholar

  • 112.

    Montserrat E. Treatment of chronic lymphocytic leukemia: achieving minimal residual disease-negative status as a goal. J Clin Oncol 2005; 23:2884–5.CrossrefGoogle Scholar

  • 113.

    Szczepański T, van Dongen JJ. Detection of minimal residual disease. In: Henderson ES, Lister TA, Greaves MF, editors. Leukemia. Philadelphia, PA: WB Saunders, 2002:249–83.Google Scholar

  • 114.

    van Dongen JJ, Breit TM, Adriaansen HJ, Beishuizen A, Hooijkaas H. Detection of minimal residual disease in acute leukemia by immunological marker analysis and polymerase chain reaction. Leukemia 1992; 6:47–59.Google Scholar

  • 115.

    Campana D, Pui CH. Detection of minimal residual disease in acute leukemia: methodologic advances and clinical significance. Blood 1995; 85:1416–34.Google Scholar

  • 116.

    Campana D. Determination of minimal residual disease in leukaemia patients. Br J Haematol 2003; 121:823–38.CrossrefGoogle Scholar

  • 117.

    Van Lochem EG, Wiegers YM, van den Beemd R, Hahlen K, van Dongen JJ, Hooijkaas H. Regeneration pattern of precursor-B-cells in bone marrow of acute lymphoblastic leukemia patients depends on the type of preceding chemotherapy. Leukemia 2000; 14:688–95.CrossrefGoogle Scholar

  • 118.

    van Wering ER, van der Linden-Schrever BE, Szczepański T, Willemse MJ, Baars EA, van Wijngaarde-Schmitz HM, et al. Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia: implications for monitoring of minimal residual disease. Br J Haematol 2000; 110:139–46.CrossrefGoogle Scholar

  • 119.

    Chen JS, Coustan-Smith E, Suzuki T, Neale GA, Mihara K, Pui CH, et al. Identification of novel markers for monitoring minimal residual disease in acute lymphoblastic leukemia. Blood 2001; 97:2115–20.CrossrefGoogle Scholar

  • 120.

    Lee RV, Braylan RC, Rimsza LM. CD58 expression decreases as nonmalignant B cells mature in bone marrow and is frequently overexpressed in adult and pediatric precursor B-cell acute lymphoblastic leukemia. Am J Clin Pathol 2005; 123:119–24.CrossrefGoogle Scholar

  • 121.

    Veltroni M, De Zen L, Sanzari MC, Maglia O, Dworzak MN, Ratei R, et al. Expression of CD58 in normal, regenerating and leukemic bone marrow B cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia. Haematologica 2003; 88:1245–52.Google Scholar

  • 122.

    Lucio P, Parreira A, van den Beemd MW, van Lochem EG, van Wering ER, Baars E, et al. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia 1999; 13:419–27.CrossrefGoogle Scholar

  • 123.

    Ciudad J, San Miguel JF, Lopez-Berges MC, Garcia Marcos MA, Gonzalez M, Vazquez L, et al. Detection of abnormalities in B-cell differentiation pattern is a useful tool to predict relapse in precursor-B-ALL. Br J Haematol 1999; 104:695–705.CrossrefGoogle Scholar

  • 124.

    Dworzak MN, Fritsch G, Fleischer C, Printz D, Froschl G, Buchinger P, et al. Comparative phenotype mapping of normal vs. malignant pediatric B-lymphopoiesis unveils leukemia-associated aberrations. Exp Hematol 1998; 26:305–13.Google Scholar

  • 125.

    Ciudad J, San Miguel JF, Lopez-Berges MC, Vidriales B, Valverde B, Ocqueteau M, et al. Prognostic value of immunophenotypic detection of minimal residual disease in acute lymphoblastic leukemia. J Clin Oncol 1998; 16:3774–81.CrossrefGoogle Scholar

  • 126.

    Griesinger F, Piró-Noack M, Kaib N, Falk M, Renziehausen A, Troff C, et al. Leukaemia-associated immunophenotypes (LIAP) are observed on 90% of adult and childhood acute lymphoblastic leukaemia: detection in remission marrow predicts outcome. Br J Haematol 1999; 105:241–55.CrossrefGoogle Scholar

  • 127.

    Borowitz MJ, Pullen DJ, Shuster JJ, Viswanatha D, Montgomery K, Willman CL, et al. Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children's Oncology Group study. Leukemia 2003; 17:1566–72.CrossrefGoogle Scholar

  • 128.

    Gaipa G, Basso G, Maglia O, Leoni V, Faini A, Cazzaniga G, et al. Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection. Leukemia 2005; 19:49–56.Google Scholar

  • 129.

    van der Sluijs-Gelling AJ, van der Velden VH, Roeffen ET, Veerman AJ, van Wering ER. Immunophenotypic modulation in childhood precursor-B-ALL can be mimicked in vitro and is related to the induction of cell death. Leukemia 2005; 19:1845–7.CrossrefGoogle Scholar

  • 130.

    Borowitz MJ, Pullen DJ, Winick N, Martin PL, Bowman WP, Camitta B. Comparison of diagnostic and relapse flow cytometry phenotypes in childhood acute lymphoblastic leukemia: implications for residual disease detection: a report from the children's oncology group. Cytometry B Clin Cytom 2005; 68:18–24.CrossrefGoogle Scholar

  • 131.

    van Wering ER, Beishuizen A, Roeffen ET, van der Linden-Schrever BE, Verhoeven MA, Hahlen K, et al. Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia. Leukemia 1995; 9:1523–33.Google Scholar

  • 132.

    van Dongen JJ, Szczepański T, de Bruijn MAC, Van den Beemd MW, de Bruin-Versteeg S, Wijkhuijs JM, et al. Detection of minimal residual disease in acute leukemia patients. Cytokines Mol Ther 1996; 2:121–33.Google Scholar

  • 133.

    Porwit-MacDonald A, Bjorklund E, Lucio P, van Lochem EG, Mazur J, Parreira A, et al. BIOMED-1 concerted action report: flow cytometric characterization of CD7+ cell subsets in normal bone marrow as a basis for the diagnosis and follow-up of T cell acute lymphoblastic leukemia (T-ALL). Leukemia 2000; 14:816–25.CrossrefGoogle Scholar

  • 134.

    Dworzak MN, Froschl G, Printz D, Zen LD, Gaipa G, Ratei R, et al. CD99 expression in T-lineage ALL: implications for flow cytometric detection of minimal residual disease. Leukemia 2004; 18:703–8.CrossrefGoogle Scholar

  • 135.

    Cabezudo E, Matutes E, Ramrattan M, Morilla R, Catovsky D. Analysis of residual disease in chronic lymphocytic leukemia by flow cytometry. Leukemia 1997; 11:1909–14.CrossrefGoogle Scholar

  • 136.

    Rawstron AC, Kennedy B, Evans PA, Davies FE, Richards SJ, Haynes AP, et al. Quantitation of minimal disease levels in chronic lymphocytic leukemia using a sensitive flow cytometric assay improves the prediction of outcome and can be used to optimize therapy. Blood 2001; 98:29–35.CrossrefGoogle Scholar

  • 137.

    Sanchez ML, Almeida J, Vidriales B, Lopez-Berges MC, Garcia-Marcos MA, Moro MJ, et al. Incidence of phenotypic aberrations in a series of 467 patients with B chronic lymphoproliferative disorders: basis for the design of specific four-color stainings to be used for minimal residual disease investigation. Leukemia 2002; 16:1460–9.CrossrefGoogle Scholar

  • 138.

    Hermine O, Haioun C, Lepage E, d'Agay MF, Briere J, Lavignac C, et al. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Blood 1996; 87:265–72.Google Scholar

About the article

Corresponding author: Prof. J.J.M. van Dongen, MD, PhD, Department of Immunology, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands Phone: +31-10-4088094, Fax: +31-10-4089456,


Received: 2006-02-14

Accepted: 2006-03-17

Published Online: 2006-06-16

Published in Print: 2006-07-01


Citation Information: Clinical Chemistry and Laboratory Medicine (CCLM), ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2006.146.

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