Elsevier

Leukemia Research

Volume 24, Issue 8, August 2000, Pages 681-703
Leukemia Research

Review
Malignant hematopoietic cell lines: in vitro models for the study of multiple myeloma and plasma cell leukemia

https://doi.org/10.1016/S0145-2126(99)00195-2Get rights and content

Abstract

Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. The disease is progressive and always lethal characterized by the slow proliferation of malignant plasma cells in the bone marrow. Much of our current understanding of the biology of MM has been obtained by studying MM-derived cell lines. Human myeloma cell lines were shown to be suitable model systems for use in various fields of the biological sciences. However, it has proved very difficult to establish cell lines from plasma cell dyscrasias. Most reported MM cell lines have been derived from patients with advanced disease and from extramedullary sites. Nevertheless, within the last 20 years more than 100 cell lines have been established. A significant portion of this panel is partially or well characterized with regard to their cell culture, clinical, immunophenotypic, cytogenetic and functional features. Distinct immunoprofiles could be assigned to MM cell lines. All MM cell lines display chromosomal aberrations; in more than 80% of the cell lines analyzed, chromosome 14 band q32 (immunoglobulin heavy chain locus) is affected; the various types of 14q+ chromosomes showed different distributions among the MM cell lines. A large percentage of MM cell lines is constitutively interleukin-6-dependent or responsive to various cytokines. It is important to realize that not every cell line established from a patient with myeloma is a neoplastic cell line. So-called ‘myeloma cell lines’ have been previously reported and are still widely used which are in reality Epstein–Barr virus (EBV)-positive B-lymphoblastoid cell lines. The presence of the EBV-genome in residual normal B-cells provides them with a selective growth advantage after explantation. In summary, a significant number of authentic and well-characterized MM cell lines has been established and described. The availability of these bona fide MM cell lines is of great importance for the study of the biology, etiology and treatment of the disease.

Section snippets

Multiple myeloma

Multiple myeloma (MM) and the rare plasmacytoma (PCT)/plasma cell leukemia (PCL) are B-cell neoplasias characterized by the clonal expansion and accumulation of malignant plasma cells starting initially in the bone marrow. Clinically, these diseases are generally progressive, fatal and thus far except for bone marrow or stem cell transplantation incurable. Clinical manifestations include pancytopenia, hyperproteinemia, renal dysfunction, bone lesions, and immunodeficiency. Although the cause of

Malignant hematopoietic cell lines derived from MM

As experimental model systems, continuous cell lines constitute an invaluable resource for the laboratory investigation of neoplastic diseases [19], [20], [21], [22], [23], [24], [25], [26], [27]. Screening the literature, we found that 112 MM cell lines had been established (not counting simultaneous or serial sister cell lines or subclones). A large panel of these cell lines has been well characterized and described (Table 1). However, the majority of these cell lines are insufficiently or

MM cell lines versus EBV+ B-LCLs

Continuous cell lines have been established from a range of human lymphoid neoplasias, but the cells of the most differentiated lymphoid malignancy, the plasma cell dyscrasias, seem to be the most difficult of human cells to maintain in continuous culture. Despite some unconfirmed and presumably non-reproducible reports on the high incidence of MM cell line establishment, the success rate of growing MM cell lines in continuous culture is rather low (Table 6).

Some putative MM cell lines have had

Conclusions

A distinguishing property of MM cell lines is that instead of undergoing apoptosis, they proliferate continuously in culture as developmentally arrested malignant cells. This feature makes MM cell lines ideally suited for genetic and cell biological studies. But overall, the enormous value to biological research of cell lines that can be continuously cultured in vitro needs no emphasis. Some controversy exists, however, for tumor-derived cell lines with regard to the extent to which

Acknowledgements

Both authors contributed equally to the concept, design and drafting of the article.

References (123)

  • L. Pegoraro et al.

    The human myeloma cell line LP-1: a versatile model in which to study early plasma-cell differentiation and c-myc activation

    Blood

    (1989)
  • A.F. Gazdar et al.

    Establishment and characterization of a human plasma cell myeloma culture having a rearranged cellular myc proto-oncogene

    Blood

    (1986)
  • X.G. Zhang et al.

    Reproducible obtaining of human myeloma cell lines as a model for tumor cell study in human multiple myeloma

    Blood

    (1994)
  • J. Hardin et al.

    Interleukin-6 prevents dexamethasone-induced myeloma cell death

    Blood

    (1994)
  • M. Goldstein et al.

    Phenotyic and functional analysis of B-cell lines from patients with multiple myeloma

    Blood

    (1985)
  • Y. Shima et al.

    Myeloma cells express Fas antigen/APO-1 (CD95) but only some are sensitive to anti-Fas antibody resulting in apoptosis

    Blood

    (1995)
  • G. Stranks et al.

    Deletions and rearrangements of CDKN2 in lymphoid malignancy

    Blood

    (1995)
  • H. Matsuzaki et al.

    Establishment and characterization of an amylase-producing human myeloma cell line

    Blood

    (1988)
  • T. Goto et al.

    A novel membrane antigen selectively expressed on terminally differentiated human B-cells

    Blood

    (1994)
  • S. Ogawa et al.

    Homozygous loss of the cyclin-dependent kinase 4-inhibitor (p16) gene in human leukemias

    Blood

    (1994)
  • C. Duperray et al.

    Phenotypic analysis of human myeloma cell lines

    Blood

    (1989)
  • M. Chesi et al.

    Dysregulation of cyclin D1 by translocation into an IgH gamma switch region in two multiple myeloma cell lines

    Blood

    (1996)
  • J.K. Hitzler et al.

    Role of interleukin-6 in the proliferation of human multiple myeloma cell lines OCI-My1 to 7 established from patients with advanced stage of the disease

    Blood

    (1991)
  • B. Klein et al.

    Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma

    Eur. Cytokine Net.

    (1990)
  • F. Caligaris-Cappio et al.

    Bone marrow microenvironment and the progression of multiple myeloma

    Leuk. Lymph.

    (1992)
  • F. Mandelli et al.

    Biology and treatment of multiple myeloma

    Curr. Opin. Oncol.

    (1992)
  • I. Van Riet et al.

    The involvement of adhesion molecules in the biology of multiple myeloma

    Leuk. Lymph.

    (1993)
  • B. Barlogie et al.

    Multiple myeloma: recent developments in molecular and cellular biology

    Curr. Top. Microbiol. Immunol.

    (1995)
  • L.M. Pilarski et al.

    Circulating clonotypic B-cells in the biology of multiple myeloma: Speculations on the origin of myeloma

    Leuk. Lymph.

    (1996)
  • G. Cook et al.

    The role of adhesion molecules in multiple myeloma

    Acta Haematol.

    (1997)
  • M.M. Oken

    Multiple myeloma: prognosis and standard treatment

    Cancer Invest.

    (1997)
  • G.B. Zulian

    Multiple myeloma: clinical evaluation of plasma cell lymphoproliferative disorders and initial management

    Semin. Hematol.

    (1997)
  • R. Greil et al.

    On the role and significance of Fas (Apo-1/CD95) ligand (FasL) expression in immune privileged tissues and cancer cells using multiple myeloma as a model

    Leuk. Lymph.

    (1998)
  • J.F. San Miguel et al.

    Treatment of multiple myeloma

    Haematologica

    (1999)
  • K. Nilsson

    Human B-lymphoid cell lines

    Human Cell.

    (1992)
  • K. Nilsson

    The control of growth in human multiple myeloma cell lines

  • Y. Matsuoka et al.

    Production of free light chains of immunoglobulin by a hematopoietic cell line derived from a patient with multiple myeloma

    Proc. Soc. Exp. Biol. Med.

    (1967)
  • K. Nilsson et al.

    Established immunoglobulin producing myeloma (IgE) and lymphoblastoid (IgG) cell lines from an IgE myeloma patient

    Clin. Exp. Immunol.

    (1970)
  • H.T. Hassan et al.

    Interleukins and colony stimulating factors in human myeloid leukemia cell lines

    Leuk. Lymph.

    (1995)
  • H.G. Drexler et al.

    Cytokine response profiles of human myeloid factor-dependent leukemia cell lines

    Leukemia

    (1997)
  • H.G. Drexler

    Review of alterations of the cyclin-dependent kinase inhibitor INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells

    Leukemia

    (1998)
  • H.G. Drexler et al.

    Lymphoma cell lines: In vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas)

    Leukemia

    (1998)
  • H.G. Drexler et al.

    Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia

    Leuk. Res.

    (1999)
  • Drexler HG. Malignant hematopoietic cell lines: in vitro models for the study of myelodysplastic syndromes. Leuk Res...
  • S. Shimizu et al.

    Establishment of a CD4-positive plasmacytoma cell line (AMO1)

    Leukemia

    (1993)
  • D.F. Jelinek et al.

    Coexistence of aneuploid subclones within a myeloma cell line that exhibits clonal immmunoglobulin gene rearrangement: clinical implications

    Cancer Res.

    (1993)
  • K. Ishii et al.

    IgD myeloma presenting as a testicular tumor: establishment and characterization of an IgD-secreting myeloma cell line

    Am. J. Hematol.

    (1992)
  • M. Ohmori et al.

    A novel mature B-cell line (DOBIL-6) producing both parathyroid hormone-related protein and interleukin-6 from a myeloma patient presenting with hypercalcaemia

    Br. J. Haematol.

    (1998)
  • J.J. Westendorf et al.

    Establishment and characterization of three myeloma cell lines that demonstrate variable cytokine responses and abilities to produce autocrine interleukin-6

    Leukemia

    (1996)
  • M.S. Hamilton et al.

    Characterization of a new IgG lambda myeloma plasma cell line (EJM): a further tool in the investigation of the biology of multiple myeloma

    Br. J. Haematol.

    (1990)
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