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Blood, 1 December 2000, Vol. 96, No. 12, pp. 3880-3886
NEOPLASIA
The interleukin-6 receptor alpha-chain (CD126) is
expressed by neoplastic but not normal plasma cells
Andy C. Rawstron,
James A. L. Fenton,
John Ashcroft,
Anne English,
Richard A. Jones,
Stephen J. Richards,
Guy Pratt,
Roger Owen,
Faith E. Davies,
J. Anthony Child,
Andrew S. Jack, and
Gareth Morgan
From the Haematological Malignancy Diagnostic Service,
Department of Haematology, Leeds General Infirmary, Leeds, United
Kingdom.
Interleukin-6 (IL-6) is reported to be central to the pathogenesis
of myeloma, inducing proliferation and inhibiting apoptosis in
neoplastic plasma cells. Therefore, abrogating IL-6 signaling is of
therapeutic interest, particularly with the development of humanized
anti-IL-6 receptor (IL-6R) antibodies. The use of such antibodies
clinically requires an understanding of IL-6R expression on neoplastic
cells, particularly in the cycling fraction. IL-6R expression levels
were determined on plasma cells from patients with myeloma (n = 93)
and with monoclonal gammopathy of undetermined significance (MGUS) or
plasmacytoma (n = 66) and compared with the levels found on normal
plasma cells (n = 11). In addition, 4-color flow cytometry was used
to assess the differential expression by stage of differentiation and
cell cycle status of the neoplastic plasma cells. IL-6R alpha chain
(CD126) was not detectable in normal plasma cells, but was expressed in
approximately 90% of patients with myeloma. In all groups, the
expression levels showed a normal distribution. In patients with MGUS
or plasmacytoma, neoplastic plasma cells expressed significantly higher
levels of CD126 compared with phenotypically normal plasma cells from the same marrow. VLA-5 "immature" plasma cells showed
the highest levels of CD126 expression, but "mature"
VLA-5+ myeloma plasma cells also overexpressed CD126 when
compared with normal subjects. This study demonstrates that CD126
expression is restricted to neoplastic plasma cells, with little or no
detectable expression by normal cells. Stromal cells in the bone marrow
microenvironment do not induce the overexpression because neoplastic
cells express higher levels of CD126 than normal plasma cells from the
same bone marrow in individuals with MGUS.
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