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Hodgkin's disease and anaplastic large cell lymphoma revisited

II. From cytokines to cell lineage


The true identity of Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells has been a subject of controversy for decades. Those who believe that Hodgkin's disease (HD) is a heterogeneous disease may consider it to constitute lymphomas of various origins. However, this theory seems incompatible with the finding of similar phenotypic, biologic, and immunologic properties among most HD. We believe that, in the majority of cases, HD, except for LP and some LD-type HD, is a homogeneous disease despite differences in the degree of fibrosis and/or cellular reaction. The heterogeneity in cellular reactions is a result of secretion of various cytokines by H-RS cells, which may or may not be influenced by the presence of EBV. H-RS cells, and anaplastic large cell lymphoma (ALCL) cells as well, can express a combination of cytokines and cytokine receptors that is not seen in other types of lymphomas. The unique cytokine/receptor profile (e.g. the expression of c-kit-R/CD117), along with various properties associated with H-RS/ALCL cells, leads to a hypothesis that H-RS/ALCL cells are related to similar lymphohematopoietic progenitor cells with different etiologies and somewhat limited differentiation capacity. A number of H-RS cells may differentiate with limited capacity along the B-cell pathway and may be infected by EBV, which further complicates the biologic and immunologic properties of these cells. The majority of H-RS cells may also, however, differentiate along the antigen-presenting dendritic cell pathway, as indicated by the abundant expression of restin, CD15, CD40, CD54, CD58, CD80, and CD86. The majority of ALCL cells clearly differentiate to T cells, but some may acquire B-cell or histiocyte phenotypes. The progenitor cell hypothesis may explain (1) the variable expression of CD117, CD43, and CD34 as well as the absence of CD27, CD45 and CD45RA in H-RS cells; (2) the inconsistent and irregular patterns of phenotype and genotype and the various, often very limited, degrees of differentiation among these two types of lymphoma cells; (3) the existence of secondary HD or ALCL associated with rare types of lymphomas or leukemias, or vice versa; (4) the absence of recombinase and of the B-specific transcription factors BSAP; and (5) the frequent expression of IL-7 and IL-9 in H-RS cells.

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  1. 1

    al Saati T, Delecluze HJ, Chittal S, Brousset P, Magaud JP, Dastugue N, Cohen-Knafo E, Laurent G, Rubin B, Delsol G. A novel human lymphoma cell line (Deglis) with dual B/T phenotype and gene rearrangements and containing Epstein-Barr virus genomes. Blood 80:209–216;1992.

  2. 2

    Azuma M, Ito D, Yagita H, Okumura K, Phillips JH, Lanier LL, Somoza C. B70 antigen is a second ligand for CTLA-4 and CD28. Nature 336:76–79;1993.

  3. 3

    Azuma M, Yssel H, Phillips JH, Spits H, Lanier LL. Functional expression of B7/BBI on activated T lymphocytes. J Exp Med 177:845–850;1993.

  4. 4

    Banchereau J, Rousset F. Human B lymphocytes: property, proliferation, and differentiation. Adv Immunol 52:135–262;1992.

  5. 5

    Banks PM, Metter J, Allred DC. Anaplastic large cell (Ki-1) lymphoma with histiocytic phenotype simulating carcinoma. Am J Clin Pathol 94:445–452;1990.

  6. 6

    Barberis A, Eidenhorn K, Vitelli L, Busslinger M. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Genes Dev 4:849–859;1990.

  7. 7

    Bargou RC, Mapara MY, Zugck C, Daniel PT, Pawlita M, Dohner H, Dorken B. Characterization of a novel Hodgkin cell line, HD-Myz, with myelomonocytic features mimicking Hodgkin's disease in severe combined immunodeficient mice. J Exp Med 177:1257–1268;1993.

  8. 8

    Bender JG, Unverzagt KL, Walker DE, Lee W, Van Epps DE, Smith DH, Stewart CC, To LB. Identification and comparison of CD34-positive cells and their subpopulations from normal peripheral blood and bone marrow using multicolor flow cytometry. Blood 77:2591–2596;1991.

  9. 9

    Benjamin D, Sharma V, Knobloch TJ, Armitage RJ, Dayton MA, Goodwin RG. B cell IL-7: Human B cell lines constituively secrete IL-7 and express IL-7 receptors. J Immunol 152:4749–4757;1994.

  10. 10

    Bitter MA, Franklin WA, Larson RA, McKeithan TW, Rubin CM, Le Beau MM, Stephens JK, Vardiman JW. Morphology in Ki-1 (CD30)-positive non-Hodgkin's lymphoma is correlated with clinical features and the presence of a unique chromosomal abnormality, t(2;5)(p23;q35). Am J Surg Pathol 14:305–316;1990.

  11. 11

    Borowitz MJ, Shuster JJ, Civin CI, Carroll AJ, Look AT, Behm FG, Land VJ, Pullen DJ, Crist WM. Prognostic significance of CD34 expression in childhood B-precursor acute lymphocytic leukemia: a pediatric oncology group study. J Clin Oncol 8:1389–1398;1990.

  12. 12

    Bowen MA, Olsen KJ, Cheng L, Avila D, Podack ER. Functional effects of CD30 on a large granlar lymphoma cell line, YT: Inhibition of cytotoxicity, regulation of CD28 and IL-2R, and induction of homotypic aggregation. J Immunol 151:5896–5906;1993.

  13. 13

    Branch MA, Burhing HJ, Grub HG, Ashman LK, Ludwig WF, Mertelsmann RH, Herrmann F. Functional expression of c-kit by acute myelogenous leukemia blasts is enhanced by tumor necrosis factor-α through posttranscriptional mRNA stabilization by a labile protein. Blood 80:1224–1230;1992.

  14. 14

    Braylan RC, Jaffe ES, Berard CW. Malignant lymphomas: Current classification and new observations. Pathol Annual 10:213–270;1975.

  15. 15

    Broxmeyer He, Maze R, Miyazawa K, Carow C, Hendrie PC, Coopers S, Hangoc G, Vadhan-Ray S, Lu L. The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. Cancer Cells 3:480–487;1991.

  16. 16

    Buckley PJ, O'Laughlin S, Komp DM. Histiocytes in familial and infection-induced/idiopathic hemophagocytic syndromes may exhibit phenotypic differences. Pediatr Pathol 12:51–66;1992.

  17. 17

    Buhring HJ, Ullrich A, Schaudt K, Muller CA, Busch FW. The product of the proto-oncogene c-kit (P145c-kit) is a human bone marrow surface antigen of hematopoietic precursorc cells which is expressed on a subset of acute nonlymphoblastic leukemic cells. Leukemia 5:854–860;1991.

  18. 18

    Byrne GE Jr, Rappaport H. Malignant histiocytosis. Gann Mono Cancer Res 15:145–162;1973.

  19. 19

    Carbone A, Gloghini A, De Re V, Tamaro P, Boiocchi M, Volpe R. Histopathologic, immunophenotypic, and genotypic analysis of Ki-1 anaplastic large cell lymphomas that express histiocyte-associated antigens. Cancer 66:2547–2556;1990.

  20. 20

    Carbone A, Gloghini A, Gattei V, Aldinucci D, Degan M, De Paoli P, Zagonel V, Pinto A. Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines. Blood 85:780–789;1995.

  21. 21

    Carbone A, Gloghini A, Volpe R. Paraffin section immunohistochemistry in the diagnosis of Hodgkin's disease and anaplastic large cell lymphoma (CD30+) lymphomas. Virchows Arch [A] 420:527–532;1992.

  22. 22

    Carbone A, Gloghini A, Volpe R, Pinto A. KP1 (CD68)-positive large cell lymphoma: A histopathologic and immunophenotypic characterization of 12 cases. Hum Pathol 24:886–896;1993.

  23. 23

    Caux C, Massacrier C, Vanbervliet B, Dubois B, van Kooten C, Durand I, Banchereau J. Activation of human dendritic cells through CD40 cross-linking. J Exp Med 180:1263–1272;1994.

  24. 24

    Caux C, Vanbervliet B, Massacrier C, Azuma M, Okumura K, Lanier LL, Banchereau J. B70/N7-2 is identical to CD86 and is the major functional ligand for CD28 expressed on human dendritic cells. J Exp Med 180:1841–1848;1994.

  25. 25

    Clark EA. CD40 — A cytokine receptor in search of a ligand. Tissue Antigens 36:33–36;1990.

  26. 26

    Dalloul A, Laroche L, Bagot M, Mossalayi MD, Fourcade C, Thacker DJ, Hogge DE, Merle-Beral H, Debre P, Schmitt C. Interleukin-7 is a growth factor for Sezary lymphoma cells. J Clin Invest 90:1054–1060;1992.

  27. 27

    Daus H, Trümper L, Roth J, von Bonin F, Möller P, Gause A, Pfreundshuh M. Hodgkin's and Reed-Sternberg cells do not carry T-cell receptor γ gene rearrangements: Evidence from single-cell polymerase chain reaction examination. Blood 85:1590–1595;1995.

  28. 28

    Davidson WF, Pierce JH, Rudikoff S, Morse HC III. Relationships between B cell and myeloid differentiation. Studies with a B lymphocyte progenitor line, HAFTL-1. J Exp Med 168:389–407;1988.

  29. 29

    Delabie J, Ceuppens JL, Vandenberghe P, de Boer M, Coorevits L, De Wolf-Peeters C. The B7/BB1 antigen is expressed by Reed-Sternberg cells of Hodgkin's disease and contributes to the stimulating capacity of Hodgkin's disease-derived cell lines. Blood 82:2845–2852;1993.

  30. 30

    Delabie J, Shipman R, Bruggen J, De Stropper B, van Leuven F, Tarcsay L, Cerletti N, Odink K, Diehl V, Bilbe G, et al. Expression of the novel intermediate filament-associated protein restin in Hodgkin's disease and anaplastic large-cell lymphoma. Blood 80:2891–2896;1992.

  31. 31

    Delsol G, Meggetto F, Brousset P, Cohen-Knafo E, al Saati T, Rochaix P, Gorguet B, Rubin, Voigt JJ, Chittal S. Relation of follicular dendritic reticulum cells to Reed-Sternberg cells of Hodgkin's disease with emphasis on the expression of CD21 antigen. Am J Pathol 142:1729–1738;1993.

  32. 32

    Diehl V, Pfreundschuh M, Fonatsch C, Stein H, Falk M, Burrichter H, Schaadt M. Phenotypic and genotypic analysis of Hodgkin's disease derived cell lines: histopathological and clinical implications. Cancer Surv 4:399–419;1985.

  33. 33

    Downing J, Shurtleff S, Head D, Behm F, Raimondi S, Weisenburger D, Kossakowska A, Thorner P, Zielenski M, Lorenzana A, Ladanyi M, Morris S. Molecular detection of t(2;5) of non-Hodgkin's lymphoma by reverse transcriptase polymerase chain reaction (RT-PCR). Lab Invest 95:109A;1995.

  34. 34

    Drexler HG, Thiel E, Ludwig WD. Acute myeloid leukemia expressing lymphoid-associated antigens: Diagnostic incidence and prognostic significance. Leukemia 7:489–498;1993.

  35. 35

    Dürkop H, Latza U, Hummel M, Eitelbach F, Seed B, Stein H. Molecular cloning and expression of a new member of the nerve growth factor receptor family that is characteristic for Hodgkin's disease. Cell 68:421–427;1992.

  36. 36

    Ehlich A, Martin V, Muller W, Rajewsky K. Analysis of the B-cell progenitor compartment at the level of single cells. Curr Biol 4:573–583;1994.

  37. 37

    Ellis PA, Hart DN, Colls BM, Nimmo JC, Mac-Donald JE, Angus HB. Hodgkin's cells express a novel pattern of adhesion molecules. Clin Exp Immunol 90:117–123;1992.

  38. 38

    Fisher AG, Burdet C, LeMeur M, Haasner D, Gerber P, Ceredig R. Lymphoproliferative disorders in an IL-7 transgenic mouse line. Leukemia 7(suppl 2):S66–68;1993.

  39. 39

    Ford AM, Healy LE, Bennett CA, Navarro E, Spooncer E, Greaves MF. Multilineage phenotypes of interleukin-3-dependent progenitor cells. Blood 79:1962–1971;1992.

  40. 40

    Foss FM, Koc Y, Stetler-Stevenson MA, Nguyen DT, O'Brien MC, Turner R, Sausville EA. Costimulation of cutaneous T-cell lymphoma cells by interleukin-7 and interleukin-2: Potential autocrine or paracrine effectors in the Sezary syndrome. J Clin Oncol 12:326–335;1994.

  41. 41

    Freedman AS, Freeman GJ, Rhynhan K, Nadler LM. Selective induction of B7/BBI on interferon-γ stimulated monocytes: A potential mechanism for amplification of T cell activation through the CD28 pathway. Cell Immunol 137:429–437;1991.

  42. 42

    Freeman GJ, Freedman AS, Segil JM, Lee G, Whitman JF, Nadler LM. B7, a new member of the Ig superfamily with unique expression on activated and neoplastic B cells. J Immunol 143:2714–2722;1989.

  43. 43

    Freeman GJ, Gribben JG, Boussiotis VA, Ng JW, Restivo VA Jr, Lombard LA, Gray GS, Nadler LM. Cloning of B7-2: A CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 262:909–911;1993.

  44. 44

    Freudenthal PS, Steinman RM. The distinct surface of human blood dendritic cells. Proc Natl Acad Sci USA 87:7698–7703;1990.

  45. 45

    Gerhartz HH, Schmetzer H. Detection of minimal residual disease in acute myeloid leukemia. Leukemia 4:508–516;1990.

  46. 46

    Godfrey DI, Zlotnik A, Suda T. Phenotypic and functional characterization of c-kit expression during intrathymic T cell development. J Immunol 149:2281–2285;1992.

  47. 47

    Gregory CD, Kirchgens C, Edwards CF, Young LS, Rowe M, Forster A, Rabbits TH, Rickinson AB. Epstein-Barr virus-transformed human precursor B cell lines — Altered growth phenotype of lines with germi-line or rearranged but nonexpressed heavy chain genes. Eur J Immunol 17:119–1207;1987.

  48. 48

    Gruss H-J, Brach MA, Drexler G, Bross KJ, Herrmann F. Interleukin 9 is expressed by primary and cultured Hodgkin and Reed-Sternberg cells. Cancer Res 52:1026–1031;1992.

  49. 49

    Gruss H-J, Brach MA, Drexler HG, Bonifer R, Mertelsmann RH, Herrmann F. Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. Cancer Res 52:3353–3360;1992.

  50. 50

    Gruss H-J, Hirschstein D, Wright B, Ulrich D, Caligiuri MA, Strockbine L, Armitage RJ, Dower SK. Expression and function of CD40 on Hodgkin and Reed-Sternberg cells and the possible relevance for Hodgkin's disease. Blood 84;2305–2314;1994.

  51. 51

    Hanson CA, Ross CW, Schnitzer B. Anti-CD34 immunoperoxidase staining in paraffin sections of acute leukemia. Comparison with flow cytometric immunophenotyping. Hum Pathol 23:26–32;1992.

  52. 52

    Hardy RR, Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci USA 88:11550–11554;1991.

  53. 53

    Henderson AJ, Narayanan R, Collins L, Dorshkind K. Status of kappa L chain gene rearrangements and c-kit and IL-7 receptor expression in stromal cell-dependent pre-B cells. J Immunol 149:1973–1979;1992.

  54. 54

    Herbst H, Dallenbach F, Hummel M, et al. Epstein-Bar virus DNA and latent gene products in Ki-1 (CD30)-positive anaplastic large cell lymphomas. Blood 78:1–10;1991.

  55. 55

    Herbst H, Niedobitek G, Kneba M, Hummel M, Finn R, Anagnostopoulos I, Bergholz M, Krieger G, Stein H. High incidence of Epstein-Barr virus genomes in Hodgkin's disease. Am J Pathol 137:13–18;1990.

  56. 56

    Herbst H, Tippelmann G, Anagnostopoulos I, Gerdes J, Schwarting R, Boehm T, Pileri S, Jones DB, Stein H. Immunoglobulin and T-cell receptor gene rearrangements in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma. Dissociation between phenotype and genotype. Leuk Res 13:103–116;1989.

  57. 57

    Hirayama F, Shih JP, Awgulewitsch A, Warr GW, Clark SC, Ogawa M. Clonal proliferation of murine lymphohematopoetic progenitors in culture. Proc Natl Acad Sci USA 89:5907–5911;1992.

  58. 58

    Hodgkin T. On some morbid appearance of the absorbent glands and spleen. Med Chir Trans 17:68–114;1832.

  59. 59

    Holbrook ST, Ohls RK, Schibler KR, Yang Y-C, Christensen RD. Effect of interleukin-9 on clonogenic maturation and cell-cycle status of fetal and adult hematopoietic progenitors. Blood 77:2129–2134;1991.

  60. 60

    Horst E, Meijer CJ, Radaskiewicz T, van Dongen JJ, Pieters R, Figdor CG, Hooftman A, Pals ST. Expression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development. Leukemia 4:383–389;1990.

  61. 61

    Hsu SM. Immunohistochemistry in lymphomas: Review and outlook. Hematol Pathol 2:91–105;1988.

  62. 62

    Hsu SM, Ho YS, Hsu PL. Expression of different phenotypes in so-called true histiocytic lymphoma and malignant histiocytosis. Am J Pathol 138:1389–1404;1991.

  63. 63

    Hsu SM, Ho YS, Hsu PL. Lymphomas of true histiocytic origin: expression of different phenotypes in so-called true histiocytic lymphoma and malignant histiocytosis. Am J Pathol 138:1389–1404;1991.

  64. 64

    Hsu SM, Hsu PL. The nature of Reed-Sternberg cells: Phenotype, genotype, and other properties. Crit Rev Oncogen 5:213–246;1994.

  65. 65

    Hsu SM, Hsu PL. Autocrine and paracrine function of cytokines in malignant lymphomas. Biomed Pharmacother 48:433–444;1994.

  66. 66

    Hsu SM, Hsu PL. Phenotypic expression of Hodgkin's disease. Relationship to biologic, immunonologic and functional properties of Reed-Sternberg Cells. In: Garrett CT, Sell S, eds. Cellular Cancer Markers. Totowa, Humana, 289–334;1995.

  67. 67

    Hsu SM, Hsu PL, Mulshine J, Ho YS, Ge ZH, Huang L. Ultrastructural and biochemical studies of Leu M1 antigens in granulocytes and H-RS cells in Hodgkin's disease. J Natl Cancer Inst 77:363–370;1986.

  68. 68

    Hsu SM, Jaffe ES. Leu M1 and peanut agglutinin stain the neoplastic cells of Hodgkin's disease. Am J Clin Pathol 82:29–32;1984.

  69. 69

    Hsu SM, Waldron JA Jr, Hsu PL, Hough AJ Jr. Cytokines and malignant lymphomas: A review and prospective evaluation. Hum Pathol 24:1040–1057;1993.

  70. 70

    Hsu SM, Waldron J, Xie SS, Hsu PL. Hodgkin's disease and anaplastic large cell lymphoma revisited. I. Unique cytokine and cytokine receptor profile distinguished from that of non-Hodgkin's lymphomas. J Biomed Sci 2:302–313;1995.

  71. 71

    Hsu SM, Xie SS, Hsu PL. Absence of a B-cell specific transcription factor, BSAP, in cultured Hodgkin's Reed-Sternberg cells. Lab Invest 68:92A;1003.

  72. 72

    Hsu SM, Xie SS, Hsu PL. The cultured Reed-Sternberg cells HDLM-1 and KM-H2 can be induced to become histiocyte-like cells. H-RS cells are not derived from lymphocytes. Am J Pathol 137:353–367;1990.

  73. 73

    Hu ZB, Ma W, Uphoff CC, Quentmeier H, Drexler HG. c-kit expression in human leukemia cell lines. Blood 83:2133–2144;1994.

  74. 74

    Hultin LE, Hausner MA, Hultin PM, Giorgi JV. CD20 (pan-B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes. Cytometry 14:196–204;1993.

  75. 75

    Inaba K, Witmer-Pack M, Inaba M, Hathcock KS, Sakuta H, Azuma M, Yagita H, Okumura K, Linsley PS, Ikehara S, Muramatsu S, Hodes RJ, Steiman RM. The tissue distribution of the B7-2 costimulator factor in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J Exp Med 180:1849–1860;1994.

  76. 76

    Jaffe ES. Malignant histiocytosis and true histiocytic lymphomas. In Jaffe ES, ed. Surgical Pathology of the Lymph Nodes and Related Organs. Philadelphia, Saunders, 381–411;1985.

  77. 77

    Kadin ME. The spectrum of Ki-1+ cutaneous lymphomas. In: van Vloten WA, Willemze R, Vejlsgaard GL, et al, eds. Current Problems in Dermatology. Cutaneous Lymphoma. Basel, Karger, 19:132;1990.

  78. 78

    Katamine S, Ostu M, Tsda K, Tsuchiya S, Sato T, Ishida N, Honjo T, Ono Y. Epstein-Barr virus transforms precursor B cell even before immunoglobulin gene rearrangements. Nature 309:369–372;1984.

  79. 79

    Kato K, Radbruch A. Isolation and characterization of CD34+ hematopoietic stem cells from human peripheral blood by high-gradient magnetic cell sorting. Cytometry 14:384–392;1993.

  80. 80

    Kelleher K, Bean K, Clark SC, Leung W-Y, Yang-Feng TL, Chen JW, Lin P-F, Luo W, Yang Y-C. Human interleukin-9: Genomic sequence, chromosomal location, and sequences essential for its expression in human T-cell leukemia virus (HTLV)-I-transformed human T cells. Blood 77:1436–1441;1991.

  81. 81

    Kita K, Shirakawa S, Kamada N. Cellular characterization of acute myeloblastic leukemia associated with t(8;21)(q22;q22): The Japanese cooperative group of leukemia/lymphoma. Leuk Lymphoma 13:229–234;1994.

  82. 82

    Knecht H, Joske DJ, Emery-Goodman A, Bachmann E, Bachmann F, Odermatt BF. Expression of human recombination activating genes (RAG-1 and RAG-2) in Hodgkin's disease. Blood 80:2867–2872;1992.

  83. 83

    Korkolopoulou P, Cordell J, Jones M, Kaklamanis L, Tsenga A, Gatter KC, Mason DY. The expression of the B-cell marker mb-1 (CD79a) in Hodgkin's disease. Histopathology 24:511–515;1994.

  84. 84

    Kozmik Z, Wang S, Dörfler P, Adams B, Busslinger M. The promoter of the CD19 gene is a target for the B-cell-specific transcription factor BSAP. Mol Cell Biol 12:2662–2669;1992.

  85. 85

    Küppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R, Hansmann M-L. Hodgkin's disease: Hodgkin's and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci USA 91:10962–10966;1994.

  86. 86

    Kuzu I, Delsol G, Jones M, Gatter KC, Mason DY. Expression of the Ig-associated heterodimer (mb-1 and B29) in Hodgkin's disease. Histopathology 22:141–144;1993.

  87. 87

    Lee BL, Cumano A, Iscove NN, Paige CJ. Stromal cell independent growth of bipotent B cell-macrophage precursors from murine fetal liver. Int Immunol 6:401–407;1994.

  88. 88

    Lemoli RM, Fogli M, Fortuna A, Amabile M, Bonsi L, Gamberi B, Martinelli G, Ferrari S, Bagnara GP, Tura S. Expression and stimulatory activity of interleukin-9 (IL-9) in human myeloid cells. Blood 84:53a;1994.

  89. 89

    Lenz A, Heine M, Schuler G, Romani N. Human and murine dermis contain dendritic cells: Isolation by means of a novel method and phenotypical and functional characterization. J Clin Invest 92:2587–2596;1993.

  90. 90

    Leoncini L, Del Vecchio MT, Kraft R, et al. Hodgkin's disease and CD30-positive anaplastic large cell lymphmas — a continuous spectrum of malignant disorder. A quantitative morphometric and immunohistologic study. Am J Pathol 137:1047–1057;1990.

  91. 91

    Leukocyte Typing IV (Vienna). In: Knapp W, ed. White Cell Differentiation antigens. London, Oxford University Press, 452;1989.

  92. 92

    Lindhout E, Lakeman A, Mevissen ML, de Groot C. Functionally active Epstein-Barr virus-transformed follicular dendritic cell-like cell lines. J Exp Med 179:1174–1184;1994.

  93. 93

    Macaulay WL. Lymphomatoid papulosis. A continuing self-healing eruption, clincally-benign histologically-malignant. Arch Dermatol 97:23–30;1968.

  94. 94

    Mallett S, Barclay AN. A new superfamily of cell surface proteins related to the nerve growth factor receptor. Immunol Today 12:220–223;1991.

  95. 95

    Masuya M, Kita K, Shimizu N, Ohishi K, Katayama N, Sekine T, Otsuji A, Miwa H, Shirakawa S. Biologic characteristics of acute leukemia after myelodysplastic syndrome. Blood 81:3388–3394;1993.

  96. 96

    Melchers F, Haasner D, Grawunder U, Kalberer C, Karasuyama H, Winkler T, Rolink AG. Roles of IgG and L chains and of surrogate H and L chains in the development of cells of the B lymphocyte lineage. Annu Rev Immunol 12:209–225;1994.

  97. 97

    Merz H, Houssiau FA, Orscheschek K, Renauld JC, Fliedner A, Herin M, Noel H, Kadin M, Mueller-Hermelink HK, van Snick J. Interleukin-9 expression in human malignant lymphoma: Unique association with Hodgkin's disease and large cell anaplastic lymphoma. Blood 78:1311–1317;1991.

  98. 98

    Miyake K, Yoshino T, Sarker AB, Termoto N, Akagi T. CD30 antigen in non-Hodgkin's lymphoma. Pathol Int 44:428–434;1994.

  99. 99

    Muench MO, Cupp J, Polakoff J, Roncarolo MG. Expression of CD33, CD38, and HLADR on human CD34+ human fetal liver progenitors with a high proliferative potential. Blood 83:3170–3181;1994.

  100. 100

    Munro JM, Freedman AS, Aster JC, Gribben JG, Lee NC, Rhynhart KK, Banchereau J, Nadler LM. In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease. Blood 83:793–798;1994.

  101. 101

    Nezelof C. The 5q35 bp chromosomal abnormality characterizes certain CD30 positive anaplastic large cell lymphomas offering a new definition of malignant histocytosis in childhood. Nouv Rev Fr Hématol 35:463–467;1993.

  102. 102

    Nickoloff BJ. The human progenitor cell antigen (CD34) is localized on endothelial cells, dermal dendritic cells, and perifollicular cells in formalin-fixed normal skin, and on proliferating endothelial cells and stromal spindleshaped cells in Kaposi's sarcoma. Arch Dermatol 127:523–529;1991.

  103. 103

    Nozawa Y, Wachi E, Tominaga K, Abe M, Wakasa H. A novel monoclonal antibody (FUN-1) identifies an activation antigen in cells of the B-cell lineage and Reed-Sternberg cells. J Pathol 169:309–315;1993.

  104. 104

    O'Grady JT, Stewart S, Lowrey J, Howie SEM, Krajewski AS. CD40 expresison in Hodgkin's disease. Am J Pathol 144:21–26;1994.

  105. 105

    Okamoto K, Yamada Y, Ogawa MS, Toyokuni S, Nakakuki Y, Ikeda H, Yoshida O, Hiai H. Abnormal bone marrow B-cell differentiation in pre-B lymphoma-prone SL/Kh mice. Cancer Res 54:399–402;1994.

  106. 106

    Orazi A, Neiman RS, Cualing H, Heerema NA, John K. CD34 immunostaining of bone marrow biopsy specimens is a reliable way to classify the phases of chronic myeloid leukemia. Am J Clin Pathol 101:426–428;1994.

  107. 107

    Osmond DG, Kim N, Manoukian R, Phillips RA, Rico-Vargas SA, Jacobsen K. Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of SCID mice. Blood 79:1695–1703;1992.

  108. 108

    Pinto AP, Gloghini A, Gattei V, Aldinucci D, Zagonel V, Carbone A. Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas. Blood 83:785–792;1994.

  109. 109

    Poppema S, Hollema H, Visser L, Vos H. Monoclonal antibodies (MT1, MT2, MB1, MB2, MB3) reactive with leukocyte subsets in paraffin-embedded tissue sections. Am J Pathol 127:418–429;1987.

  110. 110

    Quintanilla-Martinez L, Preffer F, Rubin D, Ferry JA, Harris NL. CD20+ T-cell lymphoma: Neoplastic transformation of a normal T-cell subset. Am J Clin Pathol 102:483–489;1994.

  111. 111

    Rappaport H. Tumors of the hematopoietic system. Atlas of Tumor Pathology. Washington, Armed Forces Institute of Pathology, sect 3: Fasc 8; 1966.

  112. 112

    Reauld JC, van der Lugt N, Vink A, van Roon M, Godfraind C, Warnier G, Merz H, Feller A, Berns A, van Snick J. Thymic lymphomas in interleukin 9 transgenic mice. Oncogene 9:1327–1332;1994.

  113. 113

    Rehemtulla A, Arndt A, Hart DA. Induction of plasminogen activator inhibitor type 2 expression during differentiation of human K562 cells towards a macrophage phenotype. Biochem Cell Biol 68:1337–1343;1990.

  114. 114

    Rich BE, Campos-Torres J, Tepper RI, Moreadith RW, Leder P. Cutaneous lymphoproliferation and lymphomas in interleukin 7 transgenic mice. J Exp Med 177:305–316;1993.

  115. 115

    Rolins A, Haasner D, Nishikawa S, Melchers F. Changes in frequencies of clonable pre B cells during life in different lymphoid organs of mice. Blood 81:2290–2300;1993.

  116. 116

    Roth J, Daus H, Trümper L, Gause A, Salamon-Looijen M, Pfreundschuh M. Detection of immunoglobulin heavy-chain gene rearrangement at the single-cell level in malignant lymphomas: No rearrangement is found in Hodgkin and Reed-Sternberg cells. Int J Cancer 57:799–804;1994.

  117. 117

    Sarker AB, Akagi T, Jeon HJ, Miyake K, Murakami I, Yoshino I, Yoshino T, Takahashi K, Nose S. Bauhinia purpurea: A new paraffin section marker for Reed-Sternberg cells of Hodgkin's disease. A comparison with Leu M1 (CD15), LN2 (CD74), peanut agglutinin, and Ber-H2 (CD30). Am J Pathol 141:19–23;1992.

  118. 118

    Schmid C, Pan L, Diss T, Isaacson PG. Expression of B-cell antigens by Hodgkin's and Reed-Sternberg cells. Am J Pathol 139:701–707;1991.

  119. 119

    Schwarting R, Castello R, Moldenhauer G, Pezzutto A, von Hoegen I, Ludwig WD, Parnes JR, Dorken B. Human Lyb-2 homology CD72 is a marker for progentitor B-cell leukemias. Am J Hematol 41:151–158;1992.

  120. 120

    Shiota J, Nishimura H, Okamoto H, Yu B, Hattori S, Abe M, Okada T, Nozawa S, Tsurui H, Hirose S, et al. A unique murine CD43 epitope Lp-3, distinct distribution from another CD43 epitope S7. Cell Immunol 155:402–413;1994.

  121. 121

    Srivastava BI, Srivastava A, Srivastava MD. Phenotype, genotype and cytokine production in acute leukemia involving progenitors of dendritic Langerhans' cells. Leuk Res 18:499–511;1994.

  122. 122

    Stall AM, Adams S, Herzenberg LA, Kantor AB. Characteristics and development of the murine B-1b (Ly-1 B sister) cell population. Ann NY Acad Sci 651:33–43;1992.

  123. 123

    Stein H, Dallenbach F. Diffuse large cell lymphomas of B and T cell type. In: Knowles DM, ed. Neoplastic Hematopathology. Baltimore, Williams & Wilkins, 698–710;1992.

  124. 124

    Stein H, Mason DY, Gerdes J, O'Connor N, Wainscoat J, Pallesen G, Gatter K, Falini B, Delsol G, Lemke H. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: Evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66:848–858;1985.

  125. 125

    Strauchen JA, Breakstone B. Leu M-1 antigen: comparative expression in Hodgkin's disease and T cell lymphoma. Hematol Oncol 5:107–114;1987.

  126. 126

    Su I-J, Lin K-H, Chen C-J, Tien H-F, Hsieh H-C, Lin D-T, Chen J-Y. Epstein-Barr virus-associated peripheral T-cell lymphoma of activated CD8 phenotype. Cancer 66:2557–2562;1990.

  127. 127

    Traweek ST, Arber DA, Rappaport H, Brynes RK. Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases. Am J Surg Pathol 17:1011–1019;1993.

  128. 128

    Trumper LH, Brady G, Bagg A, Gray D, Loke SL, Griesser H, Wagman R, Braziel R, Gascoyne RD, Vicini S, et al. Single-cell analysis of Hodgkin's and Reed-Sternberg cells: Molecular heterogeneity of gene expression and p53 mutations. Blood 81:3097–3115;1993.

  129. 129

    Uehira M, Matsuda H, Hikita I, Skata T, Fujiwara H, Nishimoto H. The development of dermatitis infiltrated by γδ T cells in IL-7 transgenic mice. Int Immunol 5:1619–1627;1993.

  130. 130

    Uyttenhove C, Druez C, Renauld J-C, Herin M, Noel H, van Snick J. Autonomous growth and tumorigenicity induced by P40/interleukin 9 cDNA transfection of a mouse P40-dependent T cell line. J Exp Med 173:519–522;1991.

  131. 131

    Uyttenhove C, Simpson RJ, van Snick J. Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci USA 85:6934–6938;1988.

  132. 132

    van Gorp J, Jacobse KC, Proekhuizen R, Alers J, van den Twell JG, de Weger RA. Encoded latent membrane protein 1 of Epstein-Barr virus on follicular dendritic cells in residual germinal centres in Hodgkin's disease. J Clin Pathol 47:29–32;1994.

  133. 133

    Vecchi V, Burnelli R, Pileri S, Rosito P, Sabattini E, Civino A, Pericoli R, Paolucci G. Anaplastic large cell lymphoma (Ki-1+/CD30+) in childhood. Med Pediatr Oncol 21:402–410;1993.

  134. 134

    Verschuren MC, Coman-Bitter WM, Kapteijn CA, Mason DY, Brouns GS, Borst J, Drexler HG, van Dongen JJ. Transcription and protein expression of mb-1 and B29 genes in human hematopoietic malignancies and cell lines. Leukemia 7:1939–1947;1993.

  135. 135

    Wang C, Curtis JE, Geissler EN, McCulloch EA, Minden MD. The expression of the proto-oncogene c-kit in the blast cells of acute myeloblastic leukemia. Leukemia 3:699–702;1989.

  136. 136

    Warzynski MJ, Graham DM, Axtell RA, Zakem MH, Rotman RK. Low level CD20 expression on T cell malignancies. Cytometry 18:88–92;1994.

  137. 137

    Wellmann A, Clark HM, Otsuki T, Jaffe ES, Raffeld M. Detection of the t(2;5)(p23;q35) in classical anaplastic large cell lymphoma (ALCL) by reverse transcriptase chain reaction (RT-PCR). Lab Invest 95:123A;1995.

  138. 138

    Willemze R, Meyer CJLM, van Vloten WA, et al. The clinical and histological spectrum of lymphomatoid papulosis. Br J Dermatol 107:131–144;1982.

  139. 139

    Wilson MS, Weiss LM, Gatter KC, Mason DY, Dorman RF, Warnke RA. Malignant histiocytosis: A reassessment of cases previously reported in 1975 based on paraffin section immunophenotyping studies. Cancer 66:530–536;1990.

  140. 140

    Witte ON. Steel locus defines new multipotent growth factor. Cell 63:5–6;1990.

  141. 141

    Wong KF, Chan JKC, Ng CS, Lee KC, Tsang WYW, Cheung MMC. CD56 (NHK1)-positive hematolymphoid malignancies: An aggressive neoplasm featuring frequent cutaneous/mucosal involvement, cytoplasmic azurophilic granules, and angiocentricity. Hum Pathol 23:798–804;1992.

  142. 142

    Yang Y-C. Human inteleukin-9, A new cytokine in hematopoiesis. Leukemia Lymphoma 8:441–447;1992.

  143. 143

    Yoneda N, Tatsumi E, Kawano S, Matsuo Y, Minowada J, Yamaguchi N. Human recombination activating gene-1 in leukemia/lymphoma cells: Expression depends on stage of lymphoid differentiation defined by phenotype and genotype. Blood 82:207–216;1993.

  144. 144

    Yoneda N, Tatsumi E, Kawano S, Teshigawara K, Oka T, Fukuda M, Yamaguchi N. Detection of Epstein-Barr virus genome in natural-killer-like cell line, YT. Leukemia 6:136–141;1992.

  145. 145

    Zsebo KM, Williams DA, Geissler EN, Broudy VC, Martin FH, Atkins HL, Hsu RY, Birkett NC, Okino KH, Murdoch DC, Jacobsen FW, Langley KE, Smith KA, Takeishi T, Cattanach BM, Galli SJ, Suggs SV. Stem cell factor is encoded at theSI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell 63:213–224;1990.

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Hsu, S., Waldron, J., Xie, S. et al. Hodgkin's disease and anaplastic large cell lymphoma revisited. J Biomed Sci 3, 1–13 (1996).

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Key Words

  • Hodgkin's disease
  • Cytokine
  • Lymphoma