Although multiple myeloma (MM) is a neoplasm that leads affected individuals to death, little is known about why some patients survive much longer than others. In this context, we investigated the transcriptomic profile of bone marrow hematopoietic stem cells obtained from MM patients and compared the clinical outcomes of death and survival six months after bone marrow transplantation. The leukapheresis products of 39 patients with MM eligible for autologous transplantation were collected and analyzed. After extraction, the RNA was analyzed using the GeneChip Human Exon 1.0 Array method. The transcriptome profile was analyzed , and the differentially expressed signaling pathways of interest were validated. The results showed a difference in the expression of inflammation-related genes, immune response processes, and the oxidative stress pathway. The study also pointed out the involvement of the NFκB transcription factor in the possible modulation of these genes. We chose to validate molecules participating in these processes, including the cytokines TNF-α, IFN-γ, and TGF-β1; in addition, we measured the levels of oxidative stress mediators (pro-oxidant profile and the total antioxidant capacity). TNF-α levels were significantly reduced in patients who died and were over 50 years old at diagnosis, as well as in patients with plasmacytoma. Increased TNF-α was detected in patients with very high levels of β2-microglobulin. IFN-γ reduction was observed in patients with a complete response to treatment compared to those with a very good response. Patients with plasmacytoma who died also had an increased pro-oxidant profile. These data show the profile of inflammatory response markers that are altered in patients with MM who die quickly and serve as a basis for the development of future studies of markers to predict better survival in this disease.

中文翻译：

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骨髓干细胞的转录组揭示了与多发性骨髓瘤患者生存增加相关的新炎症介质

尽管多发性骨髓瘤 (MM) 是一种会导致患者死亡的肿瘤，但人们对于为什么有些患者比其他患者存活时间长得多的原因知之甚少。在此背景下，我们研究了从 MM 患者获得的骨髓造血干细胞的转录组学特征，并比较了骨髓移植后六个月死亡和生存的临床结果。收集并分析了39例符合自体移植条件的MM患者的白细胞分离产物。提取后，使用 GeneChip Human Exon 1.0 Array 方法分析 RNA。分析转录组谱，并验证感兴趣的差异表达信号通路。结果显示炎症相关基因、免疫反应过程和氧化应激途径的表达存在差异。该研究还指出 NFκB 转录因子参与了这些基因的可能调节。我们选择验证参与这些过程的分子，包括细胞因子 TNF-α、IFN-γ 和 TGF-β1；此外，我们还测量了氧化应激介质的水平（促氧化成分和总抗氧化能力）。死亡且诊断时年龄超过 50 岁的患者以及浆细胞瘤患者的 TNF-α 水平显着降低。在 β2-微球蛋白水平非常高的患者中检测到 TNF-α 增加。与反应非常好的患者相比，在对治疗完全反应的患者中观察到 IFN-γ 减少。死亡的浆细胞瘤患者的促氧化水平也有所增加。这些数据显示了快速死亡的多发性骨髓瘤患者中炎症反应标记物的变化情况，并作为未来标记物研究的发展基础，以预测这种疾病的更好生存。