Eisterer W, Bechter O, Hilbe W, van Driel M, Lokhorst H M, Thaler J, Bloem A C, Günthert U, Stauder R
Department of Internal Medicine, Division of Haematology and Oncology, University Hospital, Anichstr. 35, 6020 Innsbruck, Austria.
Leuk Res. 2001 Dec;25(12):1051-7. doi: 10.1016/s0145-2126(01)00075-3.
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.
为评估CD44变异体同工型（CD44v）在浆细胞疾病中的作用，我们分析了多发性骨髓瘤（MM）和意义未明的单克隆丙种球蛋白病（MGUS）患者骨髓（BM）活检组织、MM软组织浸润活检组织及髓外浆细胞瘤样本中的CD44v表达情况。在49例连续MM病例的87份样本中，分别有15%、7%、13%和5%的样本观察到含有3v、4v、6v或10v结构域的CD44同工型表达，但在10名正常人和11例MGUS患者中未检测到。相比之下，CD44v9显示出更广泛的表达模式，在10名正常人中有3人、11例MGUS病例中有3人在浆细胞中观察到其表达。在MM中，87份BM浸润样本中有32份（37%）检测到CD44v9，且与Durie和Salmon分期晚期（P<0.03）、疾病进展（P<0.01）及IgA亚型（P<0.01）相关。此外，在5例MM软组织浸润病例中有3例观察到CD44v9表达，其在疾病进展过程中常上调，与较短的总生存期显著相关（P<0.03），并且在多变量分析中成为独立的预后因素（分期：相对风险1.36，P<0.02；CD44v9表达：相对风险1.45，P<0.04）。这些结果证实了CD44v结构域在浆细胞疾病中的临床相关性，并将CD44v9确立为MM中新的独立预后参数。
