Cristóbal-Vargas Sara, Cuadrado Myriam, Gutiérrez Norma C
Hematology Department, University Hospital of Salamanca, IBSAL, Salamanca, Spain; Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain.
Hematology Department, University Hospital of Salamanca, IBSAL, Salamanca, Spain; Cancer Research Center-IBMCC (USAL-CSIC), Salamanca, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC, CB16/12/00233), Salamanca, Spain.
Neoplasia. 2025 Aug;66:101177. doi: 10.1016/j.neo.2025.101177. Epub 2025 May 14.
Multiple myeloma (MM) is a hematologic malignancy with high genetic complexity. The genetic alterations that drive MM have classically been classified as primary abnormalities, including IGH translocations and hyperdiploidy, and secondary abnormalities, mainly composed of 1q gains, 17p deletions and MYC rearrangements. Dysregulation of the MYC oncogene has been proposed as a key factor in disease progression from monoclonal gammopathy of undetermined significance (MGUS), smoldering MM and overt MM. MYC, a multifunctional transcription factor, is frequently activated in MM through various mechanisms, including translocations, amplifications, and overexpression, thereby contributing to the growth and survival of malignant plasma cells. The role of MYC abnormalities in the prognosis of MM remains controversial and continues to be overlooked in current prognostic indices for MM. The different methodologies used to detect MYC lesions may hinder the interpretation of the apparently contradictory results between studies analyzing the impact of these alterations on the survival of MM patients. On the other hand, the mouse models that best mimic the characteristics of human MM are those driven by MYC. In this review, we provide an overview of the MYC alterations described in MM, indicating the methodologies used to detect them and discussing their influence on patient prognosis. We also summarize the main characteristics of the genetically engineered mouse models driven by MYC. Finally, we assess the therapeutic potential of MYC inhibition in MM and the strategies currently approved for clinic use.
多发性骨髓瘤（MM）是一种具有高度遗传复杂性的血液系统恶性肿瘤。驱动MM的基因改变传统上分为原发性异常，包括IGH易位和超二倍体，以及继发性异常，主要由1q增益、17p缺失和MYC重排组成。MYC癌基因的失调被认为是从意义未明的单克隆丙种球蛋白病（MGUS）、冒烟型MM和显性MM疾病进展的关键因素。MYC是一种多功能转录因子，在MM中经常通过各种机制被激活，包括易位、扩增和过表达，从而促进恶性浆细胞的生长和存活。MYC异常在MM预后中的作用仍存在争议，并且在目前MM的预后指标中继续被忽视。用于检测MYC病变的不同方法可能会妨碍对分析这些改变对MM患者生存影响的研究之间明显矛盾结果的解释。另一方面，最能模拟人类MM特征的小鼠模型是由MYC驱动的模型。在这篇综述中，我们概述了MM中描述的MYC改变，指出了用于检测它们的方法，并讨论了它们对患者预后的影响。我们还总结了由MYC驱动的基因工程小鼠模型的主要特征。最后，我们评估了MYC抑制在MM中的治疗潜力以及目前批准用于临床的策略。
