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Malignant hematopoietic cell lines: in vitro models for the study of anaplastic large-cell lymphoma

Leukemia volume 18, pages 1569–1571 (2004)Cite this article

Continuous cell lines established from malignant hematopoietic tumors serve as both in vitro models and pathological tools. Those established from lymphomas such as Hodgkin's disease and anaplastic large-cell lymphoma (ALCL) are particularly useful since as primary cells these tumors are difficult to study in isolation. Although about a score of ALCL cell lines have been described, only a handful of authentic well-characterized examples are freely available. Hence, the establishment and characterization of a new ALCL cell line (COST) described in this issue (Lamant et al1) should prove a useful addition to this corpus.

In the 1980s, the advent of immunohistological staining of hematological tumors led to the recognition of a new entity of malignant lymphomas, first termed Ki-1 lymphoma after the monoclonal antibody Ki-1 (CD30) and now generally designated as ALCL.2 Until then, this disease had been termed in various nomenclatures as histiocytic lymphomas, malignant histiocytosis, histiocytic sarcoma and others. These lymphomas were recognized as a distinct entity among the high-grade lymphomas in the Kiel classification of non-Hodgkin's lymphomas (NHL) and were later included in the Revised European-American Lymphoma (REAL) classification and its successor the World Health Organization (WHO) classification as a type of high-grade T-/Null-cell NHL lymphoma.3, 4 The histopathological, genetic and clinical features of ALCL have been described in detail elsewhere (for informative reviews see Drexler et al,5 Stein et al,6 and Falini7). Of particular diagnostic importance is the consistent pathognomonic chromosomal alteration t(2;5)(p32;q35), which leads to the formation of a fusion gene combining parts of the genes NPM and ALK and which occurs in approximately half of the ALCL cases.8, 9 Recently, Horie et al10 have shown that NPM-ALK fusion protein blocks CD30 signaling and constitutive NF-κB activation in ALCL.

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References

  1. Lamant L, Espinos E, Duplantier M, Dastugne N, Robert A, Allouche M et al. Establishment of a novel anaplastic large cell lymphoma-cell line (COST) from a small cell variant of ALCL. Leukemia 2004, 18: 1693–1698.

    Article  CAS  PubMed  Google Scholar 

  2. Stein H, Mason DY, Gerdes J, O’Connor N, Wainscoat J, Pallesen G et al. 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 1985; 66: 848–858.

    CAS  PubMed  Google Scholar 

  3. Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML et al. Revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 1994; 84: 1361–1392.

    CAS  PubMed  Google Scholar 

  4. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J et al. 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: 3835–3849.

    Article  CAS  PubMed  Google Scholar 

  5. Drexler HG, Gignac SM, von Wasielewski R, Werner M, Dirks WG . Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas. Leukemia 2000; 14: 1533–1559.

    Article  CAS  PubMed  Google Scholar 

  6. Stein H, Foss HD, Durkop H, Marafioti T, Delsol G, Pulford K et al. CD30(+) anaplastic large cell lymphoma: a review of its histopathologic, genetic, and clinical features. Blood 2000; 96: 3681–3695.

    CAS  PubMed  Google Scholar 

  7. Falini B . Anaplastic large cell lymphoma: pathological, molecular and clinical features. Br J Haematol 2001; 114: 741–760.

    Article  CAS  PubMed  Google Scholar 

  8. Kadin ME, Morris SW . The t(2;5) in human lymphomas. Leukemia Lymphoma 1998; 29: 249–256.

    Article  CAS  PubMed  Google Scholar 

  9. Duyster J, Bai RY, Morris SW . Translocations involving anaplastic lymphoma kinase (ALK). Oncogene 2001; 20: 5623–5637.

    Article  CAS  PubMed  Google Scholar 

  10. Horie R, Watanabe M, Ishida T, Koiwa T, Aizawa S, Itoh K et al. The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kappaB activation in anaplastic large cell lymphoma. Cancer Cell 2004; 5: 353–364.

    Article  CAS  PubMed  Google Scholar 

  11. Drexler HG, Matsuo Y, MacLeod RAF . Continuous hematopoietic cell lines as model systems for leukemia–lymphoma research. Leukemia Res 2000; 24: 881–911.

    Article  CAS  Google Scholar 

  12. Nezelof C, Barbey S, Gogusev J, Terrier–Lacombe MJ . Malignant histiocytosis in childhood: a distinctive CD30-positive clinicopathological entity associated with a chromosomal translocation involving 5q35. Semin Diagn Pathol 1992; 9: 75–89.

    CAS  PubMed  Google Scholar 

  13. Gogusev J, Nezelof C . Malignant histiocytosis. Histologic, cytochemical, chromosomal, and molecular data with a nosologic discussion. Hematol Oncol Clin North Am 1998; 12: 445–463.

    Article  CAS  PubMed  Google Scholar 

  14. Herbst H, Drexler HG . CD30-positive anaplastic large cell lymphoma cell lines. In: Masters JRW, Palsson BO (eds) Human Cell Culture, Vol. III – Cancer Cell Lines Part 3: Leukemias and Lymphomas. Dordrecht: Kluwer Academic Publishers, 2000, pp 355–370.

    Google Scholar 

  15. Drexler HG (ed). The Leukemia–Lymphoma Cell Line FactsBook. San Diego: Academic Press, 2000.

    Google Scholar 

  16. Dirks WG, Zaborski M, Jager K, Challier C, Shiota M, Quentmeier H et al. The (2;5)(p23;q35) translocation in cell lines derived from malignant lymphomas: absence of t(2;5) in Hodgkin-analogous cell lines. Leukemia 1996; 10: 142–149.

    CAS  PubMed  Google Scholar 

  17. Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S . Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 1994; 9: 1567–1574.

    CAS  PubMed  Google Scholar 

  18. Barbey S, Gogusev J, Mouly H, Le Pelletier O, Smith W, Richard S et al. DEL cell line: a ‘malignant histiocytosis’ CD30+ t(5;6)(q35;p21) cell line. Int J Cancer 1990; 45: 546–553.

    Article  CAS  PubMed  Google Scholar 

  19. Kubonishi I, Sonobe H, Miyagi T, Iwahara Y, Ohyashiki JH, Ohyashiki K et al. A Ki-1 (CD30)-positive T (E+, CD4+, Ia+)-cell line, DL-40, established from aggressive large cell lymphoma. Cancer Res 1990; 50: 7682–7685.

    CAS  PubMed  Google Scholar 

  20. Del Mistro A, Leszl A, Bertorelle R, Calabro ML, Panozzo M, Menin C et al. A CD30-positive T cell line established from an aggressive anaplastic large cell lymphoma, originally diagnosed as Hodgkin's disease. Leukemia 1994; 8: 1214–1219.

    CAS  PubMed  Google Scholar 

  21. Al-Hashmi I, Decoteau J, Gruss HJ, Zielenska M, Thorner P, Poon A et al. Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: potential role of cytokines in clinical manifestations. Leukemia Lymphoma 2001; 40: 599–611.

    Article  CAS  PubMed  Google Scholar 

  22. Su IJ, Balk SP, Kadin ME . Molecular basis for the aberrant expression of T cell antigens in postthymic T cell malignancies. Am J Pathol 1988; 132: 192–198.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Kadin ME, Cavaille-Col MW, Sioutos N, Fletcher JA, Morton CC, Pastuzak W et al. Childhood Ki-1+ anaplastic large cell lymphoma: establishment and characterization of a new tumor cell line transplantable to SCID mice. Blood 1990; 76: 354a.

    Google Scholar 

  24. Schiemann WP, Pfeifer WM, Levi E, Kadin ME, Lodish HF . A deletion in the gene for transforming growth factor beta type I receptor abolishes growth regulation by transforming growth factor beta in a cutaneous T-cell lymphoma. Blood 1999; 94: 2854–2861.

    CAS  PubMed  Google Scholar 

  25. Fischer P, Nacheva E, Mason DY, Sherrington PD, Hoyle C, Hayhoe FG et al. A Ki-1 (CD30)-positive human cell line (Karpas 299) established from a high-grade non-Hodgkin's lymphoma, showing a 2;5 translocation and rearrangement of the T-cell receptor beta-chain gene. Blood 1988; 72: 234–240.

    CAS  PubMed  Google Scholar 

  26. Shimakage M, Dezawa T, Tamura S, Tabata T, Aoyagi N, Koike M et al. A Ki-1-positive cell line expressing Epstein–Barr virus antigens, established from a child with Ki-1-positive lymphoma. Intervirology 1993; 36: 215–224.

    Article  CAS  PubMed  Google Scholar 

  27. Merz H, Lange K, Gaiser T, Muller A, Kapp U, Bittner C et al. Characterization of a novel human anaplastic large cell lymphoma cell line tumorigenic in SCID mice. Leukemia Lymphoma 2002; 43: 165–172.

    Article  PubMed  Google Scholar 

  28. Su IJ, Kadin ME . Expression of growth factor/receptor genes in postthymic T cell malignancies. Am J Pathol 1989; 135: 439–445.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Rimokh R, Magaud JP, Berger F, Samarut J, Coiffier B, Germain D et al. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma (‘Ki-1 lymphoma’). Br J Haematol 1989; 71: 31–36.

    Article  CAS  PubMed  Google Scholar 

  30. Epstein AL, Kaplan HS . Biology of the human malignant lymphomas I Establishment in continuous cell culture and heterotransplantation of diffuse histiocytic lymphomas. Cancer 1974; 34: 1851–1872.

    Article  CAS  PubMed  Google Scholar 

  31. Morgan R, Smith SD, Hecht BK, Christy V, Mellentin JD, Warnke R et al. Lack of involvement of the c-fms and N-myc genes by chromosomal translocation t(2;5)(p23;q35) common to malignancies with features of so-called malignant histiocytosis. Blood 1989; 73: 2155–2164.

    CAS  PubMed  Google Scholar 

  32. Morris SW, Kirstein MN, Valentine MB, Dittmer KG, Shapiro DN, Saltman DL et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994; 263: 1281–1284.

    Article  CAS  PubMed  Google Scholar 

  33. Umiel T, Rettenmier CW, Siegel S, Ota S, Shimada H, Tran TW et al. Establishment and characterization of a human mixed-lineage, T-lymphoid/myeloid cell line (USP-91). Blood 1993; 82: 1829–1837.

    CAS  PubMed  Google Scholar 

  34. Drexler HG, Dirks WG, Matsuo Y, MacLeod RAF . False leukemia-lymphoma cell lines: an update on over 500 cell lines. Leukemia 2003; 17: 416–426.

    Article  CAS  PubMed  Google Scholar 

  35. Al-Katib A, Abubakr Y, Mohamed A, Maki A, Diurec Z, Mohammad R . Multiple mechanisms of drug resistance in anaplastic large cell lymphoma. Blood 1994; 84: 638a.

    Google Scholar 

  36. MacLeod RAF, Drexler HG . Cytogenetic characterization of tumor cell lines. In: Langdon S (ed) Cancer Cell Culture – Methods and Protocols. Totowa, NJ: Humana Press, 2004, pp 57–76.

    Google Scholar 

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  1. Department of Human and Animal Cell Cultures, DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany

    H G Drexler & R A F MacLeod

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Correspondence to H G Drexler.

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Drexler, H., MacLeod, R. Malignant hematopoietic cell lines: in vitro models for the study of anaplastic large-cell lymphoma. Leukemia 18, 1569–1571 (2004). https://doi.org/10.1038/sj.leu.2403465

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