Bal Susan, Kumar Shaji K, Fonseca Rafael, Gay Francesca, Hungria Vania Tm, Dogan Ahmet, Costa Luciano J
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.
Am J Cancer Res. 2022 Jul 15;12(7):2950-2965. eCollection 2022.
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.
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。
