Department of Clinical Pathology, Robert-Bosch-Krankenhaus, and Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany;
Blood. 2013 Dec 5;122(24):3884-91. doi: 10.1182/blood-2013-05-498329. Epub 2013 Sep 5.
MYC is a potent oncogene initially identified as the target of the t(8;14)(q24;q32) chromosome translocation in Burkitt lymphoma. MYC gene alterations have been identified in other mature B-cell neoplasms that are usually associated with an aggressive clinical behavior. Most of these tumors originate in cells that do not normally express MYC protein. The oncogenic events leading to MYC up-regulation seem to overcome the inhibitory effect of physiological repressors such as BCL6 or BLIMP1. Aggressive lymphomas frequently carry additional oncogenic alterations that cooperate with MYC dysregulation, likely counteracting its proapoptotic function. The development of FISH probes and new reliable antibodies have facilitated the study of MYC gene alterations and protein expression in large series of patients, providing new clinical and biological perspectives regarding MYC dysregulation in aggressive lymphomas. MYC gene alterations in large B-cell lymphomas are frequently associated with BCL2 or BCL6 translocations conferring a very aggressive behavior. Conversely, MYC protein up-regulation may occur in tumors without apparent gene alterations, and its association with BCL2 overexpression also confers a poor prognosis. In this review, we integrate all of this new information and discuss perspectives, challenges, and open questions for the diagnosis and management of patients with MYC-driven aggressive B-cell lymphomas.
MYC 是一种有效的致癌基因，最初被确定为 Burkitt 淋巴瘤中 t(8;14)(q24;q32)染色体易位的靶点。MYC 基因改变已在其他成熟 B 细胞肿瘤中被识别，这些肿瘤通常与侵袭性临床行为有关。这些肿瘤大多数起源于通常不表达 MYC 蛋白的细胞。导致 MYC 上调的致癌事件似乎克服了生理抑制剂（如 BCL6 或 BLIMP1）的抑制作用。侵袭性淋巴瘤经常携带额外的致癌改变，与 MYC 失调协同作用，可能抵消其促凋亡功能。FISH 探针和新的可靠抗体的发展促进了对大量患者中 MYC 基因改变和蛋白表达的研究，为侵袭性淋巴瘤中 MYC 失调提供了新的临床和生物学观点。在大 B 细胞淋巴瘤中，MYC 基因改变常与 BCL2 或 BCL6 易位相关，导致非常侵袭性的行为。相反，MYC 蛋白上调可能发生在没有明显基因改变的肿瘤中，其与 BCL2 过表达的关联也预示着不良预后。在这篇综述中，我们整合了所有这些新信息，并讨论了针对 MYC 驱动的侵袭性 B 细胞淋巴瘤患者的诊断和管理的观点、挑战和未解决的问题。
