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

To evaluate the role of CD44 variant isoforms (CD44v) in plasma cell dyscra sias, CD44v expression was analysed in bone marrow (BM) biopsies of multipl e myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS ) patients, in biopsies of soft tissue infiltration by MM and in extramedul lary 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 1 1 MGUS patients. In contrast, CD44v9 revealed a broader pattern of expressi on and was observed in plasma cells in three out of ten normal persons and in three out of I I MGUS cases. In MM, CD44v9 was detected in 32 out of 87 samples (37%) of BM infiltrates and was associated with an advanced Durie a nd Salmon stage (P < 0.03), a progressive disease (P < 0.01) and an IgA sub type (P < 0.01). Furthermore, CD44v9 expression was observed in three out o f five cases of MM soft tissue infiltrates, was often upregulated during di sease progression, was significantly correlated with a shorter overall surv ival (P < 0.03) and emerged as an independent prognostic factor in multivar iate analysis (stage: relative risk 1.36, P < 0.02; CD44v9 expression: rela tive risk 1.45, P < 0.04). These results substantiate the clinical relevanc e of CD44v domains in plasma cell disorders and establish CD44v9 as a new i ndependent prognostic parameter in MM. (C) 2001 Elsevier Science Ltd. All r ights reserved.