Hematology Unit and Romagna Transplant Network, Ravenna Hospital, 48121 Ravenna, Italy.
Department of Medical Science, University of Torino and Fondazione Ricerca Molinette, 10129 Torino, Italy.
Cells. 2020 Dec 11;9(12):2666. doi: 10.3390/cells9122666.
Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
多发性骨髓瘤（MM）是一种血液系统疾病，其特征是骨髓（BM）中恶性浆细胞（PC）的增殖和积累。尽管广泛使用大剂量化疗联合自体干细胞移植（ASCT）和新型药物（免疫调节剂、IMiDs 和蛋白酶体抑制剂），但 MM 患者的预后仍然很差。CD38 是一种多功能的细胞表面糖蛋白，具有受体和外切酶活性。骨髓瘤 PCs 上非常高且同质的 CD38 表达使其成为新型治疗策略的有吸引力的靶点。已经开发或正在开发几种针对 MM 的抗 CD38 单克隆抗体，包括达妥木单抗和伊沙妥昔单抗。在这里，我们深入研究了 CD38 的生物学、CD38 在 MM 进展中的作用及其与 BM 微环境的复杂相互作用、抗 CD38 单克隆抗体的重要性以及抗体耐药的主要机制。然后，我们回顾了一些多参数流式细胞术技术，利用 PCs 上的 CD38 抗原表达来诊断和监测 MM 患者的治疗反应。
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