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伴有t(11;14)的多发性骨髓瘤:独特生物学特性与不断演变的格局

Multiple myeloma with t(11;14): unique biology and evolving landscape.

作者信息

Bal Susan, Kumar Shaji K, Fonseca Rafael, Gay Francesca, Hungria Vania Tm, Dogan Ahmet, Costa Luciano J

机构信息

Department of Medicine, Division of Hematology Oncology, O'Neal Comprehensive Cancer Center, The University of Alabama at Birmingham Birmingham, AL, USA.

Division of Hematology, Mayo Clinic Rochester, MN, USA.

出版信息

Am J Cancer Res. 2022 Jul 15;12(7):2950-2965. eCollection 2022.

Abstract

Multiple myeloma is characterized by heterogeneity in clinical presentation, response to treatment, and importantly, patient outcomes. The translocation of chromosomes 11 and 14 [t(11;14)(q13;32)], hereafter referred to as t(11;14), is the most common primary translocation event in multiple myeloma, occurring in approximately 16%-24% of patients. Multiple myeloma harboring t(11;14) represents a unique disease subset as t(11;14)-positive myeloma cells exhibit biological features that are distinct from t(11;14)-negative myeloma cells, including overexpression of cyclin D1, higher levels of the antiapoptotic protein BCL-2, and the frequent expression of the B-cell lineage protein CD20. Additionally, t(11;14) is associated with less common clinical features, such as immunoglobulin M and light chain disease. With the evolution of the treatment landscape, the prognostic significance of t(11;14) multiple myeloma remains debatable. However, it is clear that t(11;14) multiple myeloma represents a distinct subset and a rare opportunity for targeted therapy with BCL-2 inhibition. In this review, we first describe the underlying biology of t(11;14) multiple myeloma cells, then summarize the body of literature evaluating the prognosis of patients with t(11;14) multiple myeloma, and finally discuss therapeutic implications.

摘要

多发性骨髓瘤的特点是临床表现、对治疗的反应,以及重要的患者预后存在异质性。11号和14号染色体易位[t(11;14)(q13;32)],以下简称t(11;14),是多发性骨髓瘤中最常见的原发性易位事件,约16%-24%的患者会出现。携带t(11;14)的多发性骨髓瘤代表了一个独特的疾病亚群,因为t(11;14)阳性骨髓瘤细胞表现出与t(11;14)阴性骨髓瘤细胞不同的生物学特征,包括细胞周期蛋白D1过表达、抗凋亡蛋白BCL-2水平升高,以及B细胞谱系蛋白CD20的频繁表达。此外,t(11;14)与不太常见的临床特征相关,如免疫球蛋白M和轻链病。随着治疗格局的演变,t(11;14)多发性骨髓瘤的预后意义仍存在争议。然而,很明显,t(11;14)多发性骨髓瘤代表了一个独特的亚群,也是通过抑制BCL-2进行靶向治疗的难得机会。在这篇综述中,我们首先描述t(11;14)多发性骨髓瘤细胞的潜在生物学特性,然后总结评估t(11;14)多发性骨髓瘤患者预后的文献主体,最后讨论治疗意义。

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