CD44 isoforms are differentially regulated in plasma cell dyscrasias and CD44v9 represents a new independent prognostic parameter in multiple myeloma

Eisterer, W.; Bechter, O.; Hilbe, W.; van Driel, M.; Lokhorst, H.M.; Thaler, J.; Bloem, A.C.; Günthert, U.; Stauder, R.

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Volume 25, Issue 12 , Pages 1051-1057, December 2001

CD44 isoforms are differentially regulated in plasma cell dyscrasias and CD44v9 represents a new independent prognostic parameter in multiple myeloma

W. Eisterer
- Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria
O. Bechter
- Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria
W. Hilbe
- Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria
M. van Driel
- Department of Immunology, University Hospital, Utrecht, The Netherlands
H.M. Lokhorst
- Department of Hematology, University Hospital, Utrecht, The Netherlands
J. Thaler
- Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria
A.C. Bloem
- Department of Immunology, University Hospital, Utrecht, The Netherlands
U. Günthert
- Basel Institute for Immunology, Basel, Switzerland
R. Stauder
- Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria
- Corresponding author. Tel.: +43-512-5043341; fax: +43-512-5043341

Received 16 January 2001; accepted 7 April 2001.

Abstract

To evaluate the role of CD44 variant isoforms (CD44v) in plasma cell dyscrasias, CD44v expression was analysed in bone marrow (BM) biopsies of multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) patients, in biopsies of soft tissue infiltration by MM and in extramedullary plasmacytoma samples. Expression of CD44 isoforms containing the 3v, 4v, 6v or 10v domain was observed in 15, 7, 13 and 5% of 87 samples from 49 consecutive MM cases, but could not be detected in ten normal persons or 11 MGUS patients. In contrast, CD44v9 revealed a broader pattern of expression and was observed in plasma cells in three out of ten normal persons and in three out of 11 MGUS cases. In MM, CD44v9 was detected in 32 out of 87 samples (37%) of BM infiltrates and was associated with an advanced Durie and Salmon stage (P<0.03), a progressive disease (P<0.01) and an IgA subtype (P<0.01). Furthermore, CD44v9 expression was observed in three out of five cases of MM soft tissue infiltrates, was often upregulated during disease progression, was significantly correlated with a shorter overall survival (P<0.03) and emerged as an independent prognostic factor in multivariate analysis (stage: relative risk 1.36, P<0.02; CD44v9 expression: relative risk 1.45, P<0.04). These results substantiate the clinical relevance of CD44v domains in plasma cell disorders and establish CD44v9 as a new independent prognostic parameter in MM.

Keywords: CD44, Multiple myeloma, Plasmacytoma, Tumour, Prognosis, Risk factor

Abbreviations: ALL, acute lymphocytic leukaemia, AML, acute myeloid leukaemia, BM, bone marrow, CD44s, CD44 standard isoform, CD44v, CD44 variant isoforms, CRP, C-reactive protein, EM, extramedullary plasmacytoma, LDH, serum lactic acid dehydrogenase, MGUS, monoclonal gammopathy of undetermined significance, MM, multiple myeloma, NHL, Non-Hodgkin's lymphoma