Nikesitch Nicholas, Lee James M, Ling Silvia, Roberts Tara Laurine
Ingham Institute for Applied Medical Research and School of Medicine Western Sydney University Liverpool NSW Australia.
Department of Haematology Sydney South West Pathology Service NSW Pathology Liverpool Hospital Liverpool NSW Australia.
Clin Transl Immunology. 2018 Jan 29;7(1):e1007. doi: 10.1002/cti2.1007. eCollection 2018.
Multiple myeloma (MM) is a haematological malignancy of mature antibody-secreting plasma cells. Currently, MM is incurable, but advances in drug treatments have increased patient lifespan. One of the characteristics of MM is the excessive production of monoclonal immunoglobulin (also referred to as paraprotein). This high level of protein production induces endoplasmic reticulum (ER) stress, and proteasomal degradation of the paraprotein is required to avoid ER stress-induced cell death. Consequently, proteasomal inhibitors such as bortezomib have been particularly effective therapies. Unfortunately development of resistance to bortezomib is common. In this review, we address how control of endoplasmic reticulum stress is important in the development of MM and how the unfolded protein response and its associated stress response pathways are involved in the development of bortezomib resistance.
多发性骨髓瘤（MM）是一种成熟的抗体分泌浆细胞的血液系统恶性肿瘤。目前，MM无法治愈，但药物治疗的进展延长了患者的寿命。MM的特征之一是单克隆免疫球蛋白（也称为副蛋白）的过度产生。这种高水平的蛋白质产生会诱导内质网（ER）应激，而副蛋白的蛋白酶体降解是避免ER应激诱导的细胞死亡所必需的。因此，蛋白酶体抑制剂如硼替佐米一直是特别有效的治疗方法。不幸的是，对硼替佐米产生耐药性很常见。在这篇综述中，我们探讨了内质网应激的控制在MM发展中的重要性，以及未折叠蛋白反应及其相关应激反应途径如何参与硼替佐米耐药性的发展。
