Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee 53226, WI, USA.
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee 53226, WI, USA.
Blood Rev. 2021 Mar;46:100741. doi: 10.1016/j.blre.2020.100741. Epub 2020 Aug 11.
The autonomic nervous system (ANS), which consists of antagonistic sympathetic (adrenergic) and parasympathetic (cholinergic) arms, has emerged as an important regulator of neoplastic development, yet little is known about its role in multiple myeloma (MM). Clinical findings that anti-adrenergic β-blocker intake reduces risk of disease-specific death and overall mortality in patients with MM have indicated that adrenergic input may worsen myeloma outcome. However, preclinical studies using β-adrenergic receptor agonists or antagonists produced controversial results as to whether sympathetic pathways promote or inhibit myeloma. Retrospective outcome data demonstrating that high message levels of cholinergic receptor genes predict inferior survival in the Multiple Myeloma Research Foundation CoMMpass trial suggest that parasympathetic input may drive myeloma progression in a subset of patients. Here we review the ill-defined role of the ANS in MM, put myeloma in the context of other cancers, and discuss knowledge gaps that may afford exciting research opportunities going forward.
自主神经系统（ANS）由拮抗的交感（肾上腺素能）和副交感（胆碱能）臂组成，它已成为肿瘤发展的重要调节剂，但对其在多发性骨髓瘤（MM）中的作用知之甚少。临床研究发现，抗肾上腺素能β-阻滞剂的摄入可降低 MM 患者疾病特异性死亡和总死亡率的风险，这表明肾上腺素能输入可能会使骨髓瘤的结果恶化。然而，使用β-肾上腺素能受体激动剂或拮抗剂的临床前研究对交感神经通路是促进还是抑制骨髓瘤产生了有争议的结果。前瞻性结果数据表明，胆碱能受体基因的高表达水平预示着多发性骨髓瘤研究基金会 CoMMpass 试验中较差的生存情况，这表明副交感神经输入可能会推动一部分患者的骨髓瘤进展。在这里，我们综述了自主神经系统在 MM 中的作用不明确的问题，将骨髓瘤置于其他癌症的背景下，并讨论了可能为未来提供令人兴奋的研究机会的知识空白。
