文章：

c-MYC表达增加与活跃IGH基因座重排相关：c-MYC在慢性淋巴细胞白血病中的新兴作用

Increased c-MYC Expression Associated with Active IGH Locus Rearrangement: An Emerging Role for c-MYC in Chronic Lymphocytic Leukemia

原文发布日期：6 November 2024

DOI: 10.3390/cancers16223749

类型: Article

开放获取: 是

英文摘要：

This review examines the pivotal role of c-MYC in Chronic Lymphocytic Leukemia (CLL), focusing on how its overexpression leads to increased genetic instability, thereby accelerating disease progression.MYC, a major oncogene, encodes a transcription factor that regulates essential cellular processes, including cell cycle control, proliferation, and apoptosis. In CLL cases enriched with unmutated immunoglobulin heavy chain variable (IGHV) genes,MYCis significantly overexpressed and associated with active rearrangements in theIGHimmunoglobulin heavy chain locus. This overexpression results in substantial DNA damage, including double-strand breaks, chromosomal translocations, and an increase in abnormal repair events. Consequently, c-MYC plays a dual role in CLL: it promotes aggressive cell proliferation while concurrently driving genomic instability through its involvement in genetic recombination. This dynamic contributes not only to CLL progression but also to the overall aggressiveness of the disease. Additionally, the review suggests that c-MYC’s influence on genetic rearrangements makes it an attractive target for therapeutic strategies aimed at mitigating CLL malignancy. These findings underscore c-MYC’s critical importance in advancing CLL progression, highlighting the need for further research to explore its potential as a target in future treatment approaches.

摘要翻译： 

本综述探讨了c-MYC在慢性淋巴细胞白血病（CLL）中的关键作用，重点阐述其过度表达如何导致遗传不稳定性增加，从而加速疾病进展。MYC作为重要的癌基因，编码一种调控细胞周期、增殖和凋亡等关键细胞过程的转录因子。在富含未突变免疫球蛋白重链可变区（IGHV）基因的CLL病例中，MYC显著过表达，并与IGH免疫球蛋白重链基因座的活跃重排相关。这种过表达导致大量DNA损伤，包括双链断裂、染色体易位以及异常修复事件增加。因此，c-MYC在CLL中扮演双重角色：既促进侵袭性细胞增殖，又通过参与基因重组驱动基因组不稳定性。这种动态机制不仅推动CLL进展，还加剧了疾病的整体侵袭性。此外，本综述指出c-MYC对基因重排的影响使其成为缓解CLL恶性程度的治疗策略中具有吸引力的靶点。这些发现强调了c-MYC在促进CLL进展中的关键重要性，凸显了未来需要进一步研究其作为治疗靶点的潜力。

原文链接：

Increased c-MYC Expression Associated with Active IGH Locus Rearrangement: An Emerging Role for c-MYC in Chronic Lymphocytic Leukemia