De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances.
De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances.
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DOI：
10.1016/j.clml.2020.05.003
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发表时间：
2020-06
期刊：
影响因子：
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通讯作者：
Yichen Xu;Wenji Sun;Fei Li
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文献类型：
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作者：
Yichen Xu;Wenji Sun;Fei Li
尽管其在弥漫性大B细胞淋巴瘤（DLBCL）的所有变体中的频率较低，但CD 5 +DLBCL逐渐获得了应有的关注，这是因为与没有CD 5签名的DLBCL相比，其结局较差。CD 5 +DLBCL被分类为具有难以捉摸的遗传特征的活化B细胞样（ABC）/非生殖中心B细胞样（GCB）DLBCL，并且患者通常被表征为年龄较大和女性，并且具有东部肿瘤协作组体能状态> 1、高国际预后指数评分、发展B症状的倾向，晚期疾病，中枢神经系统复发率高，骨髓受累率高。CD 5 +DLBCL预后不良的潜在机制尚未完全探讨，我们总结了报道的潜在机制，包括CD 5介导的B细胞受体（BCR）依赖性和非依赖性途径。前者涉及BCR信号传导的抑制，后者涉及白细胞介素10、Bcl-2（抗凋亡B细胞白血病/淋巴瘤2）、细胞周期蛋白D2和CXCR 4（C-X-C基序趋化因子受体4）的BCR非依赖性过表达。传统方案R-CHOP（利妥昔单抗+环磷酰胺、多柔比星、长春新碱和泼尼松）目前在CD 5 +DLBCL中的疗效不满意。较大剂量的治疗，如R-DA-EPOCH（依托泊苷、泼尼松、长春新碱、环磷酰胺和多柔比星加利妥昔单抗）、R-ACVBP（利妥昔单抗加多柔比星、环磷酰胺、长春地辛、博来霉素和泼尼松）、R-DA-EPOCH加中枢神经系统预防，可以提高CD 5 +DLBCL患者的总生存率，而异基因造血干细胞移植作为挽救治疗仍存在争议。此外，一些新的药物，如来那度胺，CXCR 4拮抗剂，布鲁顿酪氨酸激酶抑制剂，Bcl-2抑制剂和免疫治疗，已被报道有令人鼓舞的结果，并可能改善这些患者的结果。本文就CD 5 +DLBCL的生物学、发病机制及治疗作一综述。
Despite its low frequency in all variants of diffuse large B-cell lymphoma (DLBCL), CD5+DLBCL has gradually gained the attention it deserves, the result of its poorer outcomes compared to DLBCL without the CD5 signature. CD5+DLBCL is classified as activated B-cell–like (ABC)/non–germinal-center B-cell–like (GCB) DLBCL with elusive genetic features, and patients are frequently characterized as being older and female, and as having Eastern Cooperative Oncology Group performance status > 1, high International Prognostic Index score, tendency to develop B symptoms, and advanced-stage disease with high central nervous system relapse and bone marrow involvement rate. The mechanism underlying the poor prognosis in CD5+DLBCL has not been fully explored, and we summarize the reported potential mechanisms, including CD5-mediated B-cell receptor (BCR)-dependent and -independent pathways. The former involves the inhibition of BCR signaling, and the latter involves the BCR-independent overexpression of interleukin 10, Bcl-2 (antiapoptotic B-cell leukemia/lymphoma 2), cyclin D2, and CXCR4 (C-X-C motif chemokine receptor 4). The efficacy of traditional regimen R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is currently not satisfied in CD5+DLBCL. Therapies of larger doses, such as R-DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab), R-ACVBP (rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), R-DA-EPOCH plus central nervous system prophylaxis, can improve the overall survival in CD5+DLBCL patients, while allogeneic hematopoietic stem-cell transplantation still remains controversial as a salvage treatment. In addition, some novel drugs, such as lenalidomide, CXCR4 antagonists, Bruton tyrosine kinase inhibitors, Bcl-2 inhibitors, and immunotherapy, have been reported to have encouraging results and may improve the outcomes of these patients. In the present review, we comprehensively summarize the biology, mechanism, and treatment of CD5+DLBCL.