Human Myeloma Cell Lines as a Tool for Studying

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4001
CORRESPONDENCE
Human Myeloma Cell Lines as a Tool for Studying the Biology of Multiple Myeloma:
A Reappraisal 18 Years After
To the Editor:
Multiple myeloma (MM) is characterized by the expansion of
malignant plasma cells (PCs) within the bone marrow. Although
such malignant PCs can be easily identified by their high expression
of CD38 and B-B4, their purification and in vitro expansion remain
difficult. Therefore, established human myeloma cell lines (HMCL)
are still essential to study the biology of MM. Eighteen years ago,
it was elegantly documented by Nilsson' that the establishment of
continuous cell lines from the bone marrow or the peripheral blood
of MM patients actually leads to the obtention of two completely
different types of cell lines, most frequently lymphoblastoid cell
lines (LCL), which result from the immortalization of nonmalignant
B cells by Epstein-Barr virus (EBV), and true HMCL, which represent the immortalization of tumor cells sharing the same Ig gene
rearrangement as fresh tumor cells. We and others have recently reevaluated this critical point thoroughly and confirmed it?-5 Of note,
some EBVf LCL established from the bone marrow of MM patients
can produce Igs sharing the same isotype, public idiotype, and epitopic specificity (ie, anti-DNA) as the myeloma protein, although
using completely different VL, VH, and CDR sequences, showing
their complete inrelevance to the myeloma clone?
A lot of studies devoted to the biology ofMM based on the
use of several putative HMCL have recently been published. These
interesting studies pointed towards major topics related to the MM
biology. Clearly, the two types of cell lines, ie, LCL and HMCL,
have been used indiscriminately in these studies, making some of
the conclusions irrelevant to the biology of MM. Therefore, it appears very important to clearly establish the criteria for differentiating them. Based on recent phenotypic data?' the European Myeloma
Research Network examined eight discriminant surface markers
making it possible to determine the myeloma nature (or not) of the
cell lines commercially available and routinely used in the majority
of studies. Some XG HMCL recently established by ourselves have
been included? As expected, the phenotypic analysis outlined in
Table 1 shows clearly that two types of cell lines can be distinguished: (1) on the one hand, LCL, which are positive for CD19
and CD20, surface Ig, and the adhesion molecules CDlla and
CD49e. but negative for B-B4 CD38 and CD28 molecules (ARH77, I"9, HS-Sultan, and MC-CAR); and (2) on the other hand, the
other cell lines negative for CD19, CD20, CDlla, and CD49e but
positive for the antigens characterizing the HMCL, ie, B-B4, CD38
and CD28. Attention has to be focused on the fact that one of these
differentiation antigens is not sufficient to establish the nature of the
cell line but that all these markers taken together allow an accurate
conclusion. The clear-cut phenotypic dichotomy is also supported
by the EBV status and the karyotype of these two types of cell lines,
which have been previously published. Indeed, the LCL have all
been described as EBV+ and present karyotypes completely contrasting with those of HMCL,"~" which are EBV- and have many
and complex (hut recurrent) chromosomal abnormalities identical to
those of fresh tumor cells.'* Moreover, it should be noticed that no
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
4002
CORRESPONDENCE
Table 1. Comparative Phenotypic Analysis of Myeloma and Lymphoblastoid Cell Lines
Surface lg
HMCL
XG 1
XG 2
XG 6
U266
RPM1 8226
LP1
L363
OPM2
NCLH929
LCL
ARH-77
IM9
HS-Sultan
MC/CAR
CD38
6-6,
K
++
++
++
+/-
-
+++
-
+l.+/-
-
-
-
-
-
-
-
-
++
++
+
+
+++
+++
+++
++
+++
+++
h
CD28
CD19
CD20
CDlla
+
-
-
-
++
+
++
++
+
++
-
-
-
-
+
+
-
+
+
+/+l-
++
-
+
-
-
-
++
+
+
+/-
-
-
+l-
-
+
-
-
+++
+
direct proof has ever been published that the LCL harbor the same
karyotypic abnormalities and/or Ig gene rearrangements as primary
tumor cells in the patients from whom they were derived.
Considering that the LCL ARH-77, IM9, HS-Sultan, and MCCAR listed at the ATCC as HMCL have been used frequently in
recent reports to study the biology of MM (in place of HMCL), we
would like to address some concerns about the conclusions related
to the studies regarding (1) the expression of adhesion molecules by
myeloma cells and the interaction of myeloma cells with stromal
cells through these adhesion molecules; (2) the mechanisms of bone
disease in MM; (3) the role of the CD40 molecule in MM; and (4)
the role of soluble CD16 in MM as relevant to the biology of MM.
Catherine Pellat-Deceunynk
Martine Amiot
RCgis Bataille
Laboratoire d’Oncogkn2se Immunoh&matologique
Institut de Biologie
Nantes, France
Ivan Van Riet
Benjamin Van Camp
Laboratory of Hematology and Immunology
Free University of Brussels
Brussels, Belgium
Paola Omede
Mario Boccadoro
Laboratorio Divisione di Ematologia
Universita ’ Di Torino
Torino, Italy
Biomed Program (BMHI-CT93-1407)
REFERENCES
1. Nilsson K: Established cell lines as tools in the study of human
lymphoma and myeloma cell characteristics. Haematol Blood
Transfus 20:253, 1977
2. Gazdar AF, Oie HK, Kirsch IR, Hollis GF: Establishment and
characterization of a human plasma cell myeloma culture having a
rearranged cellular myc proto-oncogene. Blood 67:1542, 1986
-
-
-
-
-
+
CD49e
-
-
-
-
-
-
-
+/-
+
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
++
++
++
++
+
+++
+
+
+
+
+
+
+/-
++
+
3. Diehl V, Schaadt M, Kirchner H, Hellriegel KP, Gudat F,
Fonatsch C, Laskewitze E, Guggenheim R: Long-term cultivation
of plasma cell leukemia cells and autologous lymphoblasts (LCL)
in vitro: A comparative study. Blut 36:331, 1978
4. Goldstein M, Hoxie J, Zernbrykid D, Matthewq D, Levinson
AI: Phenotypic and functional analysis of B cell lines from patients
with multiple myeloma. Blood 66:444, 1985
5. Commes T, Clofent G, Ghanem N, Zbang XG, Lefranc MP,
Bataille R, Klein B: Analysis of the B-cell compartment in plasma
cell leukemia and multiple myeloma: Immunoglobulin gene rearrangement of EBV-infected B-cell lines. Leukemia 7:609, 1993
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mutated anti-DNA antibody bearing two systemic lupus erythematosus-related ihotypes. J Clin Invest 85:1401, 1990
7. Pellat-Deceunynck C, Bataille R, Robillard N, Harousseau JL,
Rapp MJ, Juge-Morineau N, Wijdenes J, Amiot M: Expression of
CD28 and CD40 in human myeloma cells: A comparative study
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8. Pellat-Deceunynck C, Barill6 S, Puthier D, Rapp MJ, Harousseau JL, Bataille R, Amiot M: Adhesion molecules on human myeloma cells: Significant changes in expression related to malignancy,
tumor spreading and immortalization. Cancer Res 55:3647, 1995
9. Zhang XG, Gaillard JP, Robillard N, Lu ZY, Gu ZJ, Jourdan
M, Boiron JM, Bataille R, KleinB: Reproducible obtaining of human
myeloma cell lines as a model for tumor stem cell study in human
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10. Rittz RE, Ruiz-Arguelles A, Weyl KG, Bradley AL, Weihmeir B, Jacobsen DJ, Strehlo BL: Establishment and characterization
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11. Drewinko B, Mars W, Minowada J, Burk KH, Trujillo JM:
ARH-77, an established human IgG-producing myeloma cell line.
I. Morphology, B-cell phenotypic marker profile, and expression of
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From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
1995 86: 4001-4002
Human myeloma cell lines as a tool for studying the biology of
multiple myeloma: a reappraisal 18 years after [letter]
C Pellat-Deceunynk, M Amiot, R Bataille, I Van Riet, B Van Camp, P Omede and M Boccadoro
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