Arnulf B, Lecourt S, Soulier J, Ternaux B, Lacassagne M-Noelle, Crinquette A, Dessoly J, Sciaini A-K, Benbunan M, Chomienne C, Fermand J-P, Marolleau J-P, Larghero J
Département d'Immuno-Hématologie, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis et Laboratoire EA3963, Université Paris VII, Paris, France.
Leukemia. 2007 Jan;21(1):158-63. doi: 10.1038/sj.leu.2404466. Epub 2006 Nov 9.
Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells, primarily in the bone marrow (BM). The role of the BM microenvironment in the pathogenesis of the disease has been demonstrated, especially for the survival and growth of the myeloma plasma cells. Functional characterization of the major component of the BM microenvironment, namely the recently characterized mesenchymal stem cells (MSCs), was never performed in MM. Based on a series of 61 consecutive patients, we evaluated the ability of MSCs derived from myeloma patients to differentiate into adipocytes and osteocytes, inhibit T-cell functions, and support normal hematopoiesis. MSCs phenotypic characterization and quantification of interleukin-6 (IL-6) secretion were also performed. As compared to normal MSCs, MSCs from MM patients exhibited normal phenotype, differentiation capacity and long-term hematopoietic support, but showed reduced efficiency to inhibit T-cell proliferation and produced abnormally high amounts of IL-6. Importantly, these characteristics were observed in the absence of any detectable tumor plasma cell. Chromosomal analysis revealed that MM patients MSCs were devoid of chromosomal clonal markers identified in plasma cells. MM MSCs present abnormal features that may participate in the pathogenesis of MM.
多发性骨髓瘤（MM）是一种由克隆性浆细胞增殖引起的B细胞肿瘤，主要发生于骨髓（BM）。骨髓微环境在该疾病发病机制中的作用已得到证实，尤其是对骨髓瘤浆细胞的存活和生长而言。骨髓微环境的主要成分，即最近鉴定出的间充质干细胞（MSC），在MM中从未进行过功能特性研究。基于连续61例患者，我们评估了骨髓瘤患者来源的间充质干细胞分化为脂肪细胞和骨细胞、抑制T细胞功能以及支持正常造血的能力。还进行了间充质干细胞的表型鉴定和白细胞介素-6（IL-6）分泌的定量分析。与正常间充质干细胞相比，MM患者的间充质干细胞表现出正常的表型、分化能力和长期造血支持能力，但抑制T细胞增殖的效率降低，且产生异常大量的IL-6。重要的是，在未检测到任何肿瘤浆细胞的情况下观察到了这些特征。染色体分析显示，MM患者的间充质干细胞缺乏在浆细胞中鉴定出的染色体克隆标记。MM间充质干细胞呈现出可能参与MM发病机制的异常特征。
