在多发性骨髓瘤患者中存在恶性 CD34+CD138+B7-H1+浆细胞亚群。

A subpopulation of malignant CD34+CD138+B7-H1+ plasma cells is present in multiple myeloma patients.

机构信息

INSERM, Unité 837, Institut de Recherche sur Cancer de Lille, Lille, France.

出版信息

Exp Hematol. 2010 Feb;38(2):124-31. doi: 10.1016/j.exphem.2009.11.008. Epub 2009 Dec 3.

DOI:10.1016/j.exphem.2009.11.008

PMID:19948206

Abstract

OBJECTIVE

It is generally assumed that plasma cells from multiple myeloma (MM) patients do not express the stem cell marker CD34. This assumption has led to several clinical trials based on autologous CD34(+) cell transplantation. However, the results of these trials have been disappointing.

MATERIALS AND METHODS

We investigated the presence of CD34(+) cell populations in RPMI 8226, KARPAS 417, and U266 MM cell lines in vitro and during their growth as plasmacytoma tumors in nonobese diabetic severe combined immunodeficient mice, and in plasma cells isolated from the bone marrow of 38 MM patients.

RESULTS

We showed that in both patients and cell lines, a small population of plasma cells expresses CD34. These cells display morphological characteristics of MM plasma cells, are CD19-negative, and express B7-H1 (PD-L1), a T-cell inhibitory molecule. In patients, CD34(+)CD138(+) cells expressed Ki67, a marker for proliferation. Moreover, when cells from the human myeloma cell line U266 were injected into nonobese diabetic severe combined immunodeficient mice, the U266-derived plasmacytoma tumors showed a large CD34(+)CD138(+) Ki67(+) cell population, indicating that these cells were not quiescent in vivo.

CONCLUSIONS

MM patients carry a small subpopulation of cycling CD34(+)CD138(+)B7-H1(+) plasma cells. Their presence may limit the clinical benefits of autologous CD34(+) cell transplantation.

摘要

目的

一般认为多发性骨髓瘤（MM）患者的浆细胞不表达干细胞标志物 CD34。这种假设导致了几项基于自体 CD34（+）细胞移植的临床试验。然而，这些试验的结果令人失望。

材料和方法

我们在体外研究了 RPMI 8226、KARPAS 417 和 U266 MM 细胞系以及在非肥胖型糖尿病严重联合免疫缺陷小鼠中作为浆细胞瘤生长时以及从 38 例 MM 患者骨髓中分离的浆细胞中 CD34（+）细胞群体的存在。

结果

我们表明，在患者和细胞系中，一小部分浆细胞表达 CD34。这些细胞显示 MM 浆细胞的形态特征，CD19 阴性，并表达 B7-H1（PD-L1），一种 T 细胞抑制分子。在患者中，CD34（+）CD138（+）细胞表达 Ki67，这是增殖的标志物。此外，当来自人骨髓瘤细胞系 U266 的细胞注入非肥胖型糖尿病严重联合免疫缺陷小鼠时，U266 衍生的浆细胞瘤肿瘤显示出大量的 CD34（+）CD138（+）Ki67（+）细胞群体，表明这些细胞在体内不是静止的。