Angiogenic cytokines profile in smoldering multiple myeloma: no difference compared to MGUS but altered compared to symptomatic myeloma.
Angiogenic cytokines profile in smoldering multiple myeloma: no difference compared to MGUS but altered compared to symptomatic myeloma.
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DOI：
10.12659/msm.889752
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发表时间：
2013-12-20
期刊：
影响因子：
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通讯作者：
Terpos E
中科院分区：
文献类型：
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作者：
Gkotzamanidou M;Christoulas D;Souliotis VL;Papatheodorou A;Dimopoulos MA;Terpos E
症状性多发性骨髓瘤（MM）是从无症状的前体状态演变而来的，称为意义不明的单克隆丙种球蛋白病（MGUS）和郁积性骨髓瘤（SMM）。血管生成在MM的发病机制中起着关键作用，但关于SMM中血管生成的数据非常有限。我们检测了54例SMM患者的血管生成素-1（Ang-1）、血管生成素-2（Ang-2）、血管内皮生长因子（VEGF）和血管生成素的循环水平。结果与27例MGUS患者，55例MM患者和22例健康对照进行了比较。同时检测10例SMM、10例症状性MM和10例MGUS患者的VEGF-A基因表达。在有症状的MM患者中，由于Ang-2的急剧增加，循环Ang-1/Ang-2的比率降低（p<0.001），但在SMM或MGUS患者中则没有，与对照组相比没有差异。与对照组相比，所有患者的VEGF和血管生成素均升高。然而，与SMM和MGUS相比，有症状的MM中循环VEGF较高，而血管生成素降低。VEGF-A的表达在3种患者类别之间无差异。SMM具有与MGUS相似的循环血管生成细胞因子谱，但与症状性MM相比具有改变的谱。因此，在MGUS向SMM的进展中，循环血管生成细胞因子似乎相同。相反，在有症状的骨髓瘤中，血管生成素沿着VEGF的改变有助于骨髓瘤细胞生长，支持这些分子用于开发新型抗骨髓瘤药物的靶点。
Symptomatic multiple myeloma (MM) evolves from an asymptomatic precursor state termed monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM). Angiogenesis plays a key role in the pathogenesis of MM but there are very limited data for angiogenesis in SMM. We measured the circulating levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and angiogenin in 54 patients with SMM. The results were compared with those of 27 MGUS patients, 55 MM patients, and 22 healthy controls. The expression of VEGF-A gene was also evaluated in 10 patients with SMM, 10 with symptomatic MM, and 10 with MGUS. The ratio of circulating Ang-1/Ang-2 was reduced in MM patients with symptomatic disease due to a dramatic increase of Ang-2 (p<0.001), but not in patients with SMM or MGUS, in whom it did not differ compared to controls. VEGF and angiogenin were increased in all patients compared to controls. However, circulating VEGF was higher in symptomatic MM compared to SMM and MGUS, while angiogenin was reduced. There were no differences in the expression of VEGF-A among the 3 patients categories. SMM has a circulating angiogenic cytokine profile similar to that of MGUS, but has altered profile compared to symptomatic MM. Thus, in the progression of MGUS to SMM, circulating angiogenic cytokines seem to be the same. On the contrary, in symptomatic myeloma, the alterations of angiopoietins along with VEGF contribute to myeloma cell growth, supporting the target of these molecules for the development of novel anti-myeloma agents.