The pattern of Mesenchymal stem cell expression is an independent marker of outcome in multiple myeloma

Mesenchymal stem cells (MSCs) are an essential component of the bone marrow (BM) microenvironment and have shown to support cancer evolution in multiple myeloma (MM). Despite the increasing evidence that MM MSCs differ from their healthy counterparts, little knowledge exists as to whether MSCs independently influence disease outcome. The aim of the present study was to determine the importance of MSCs in disease progression and outcome in MM. To determine the impact of MSCs on MM outcome in an in vivo system, we first identified genes from cultured MSCs that were specific to MSC expression and were not or minimally expressed in PCs or other cells present in BM aspirates. We then applied this MSC gene signature to whole BM biopsies of MM patients compared to healthy controls and determined MSC expression scores specific to MM and predictive of outcome. Molecular subgroup definitions: CD-1: CCND1/CCND3 (group 5) CD-2: CCND1/CCND3 (group 6) HY: Hyperdiploid LB: Low bone disease MF: MAF/MAFB MS: MMSET PR: Proliferation Discussion of these molecular subgroups is available in: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895543/间充质干细胞（Mesenchymal stem cells, MSCs）是骨髓（bone marrow, BM）微环境的关键组成部分，已被证实可支持多发性骨髓瘤（multiple myeloma, MM）的癌症进展。尽管越来越多的证据表明多发性骨髓瘤来源的间充质干细胞与健康对照来源的间充质干细胞存在显著差异，但目前关于间充质干细胞是否会独立影响疾病预后的认知仍十分有限。本研究旨在明确间充质干细胞在多发性骨髓瘤疾病进展与预后中的重要作用。为探究体内环境中间充质干细胞对多发性骨髓瘤预后的影响，我们首先从培养的间充质干细胞中筛选出具有间充质干细胞特异性表达特征的基因，此类基因在浆细胞（plasma cells, PCs）或骨髓抽吸物中的其他细胞内几乎不表达或仅呈微量表达。随后，我们将该间充质干细胞基因特征应用于多发性骨髓瘤患者与健康对照的全骨髓活检样本，构建了多发性骨髓瘤特异性的间充质干细胞表达评分模型，并证实该评分可有效预测患者预后。 分子亚组定义如下： CD-1：CCND1/CCND3（第5组） CD-2：CCND1/CCND3（第6组） HY：超二倍体（Hyperdiploid） LB：低骨病（Low bone disease） MF：MAF/MAFB MS：MMSET PR：增殖型（Proliferation） 上述分子亚组的详细讨论可参阅：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1895543/