Lymphocyte Development and Disease Group, Josep Carreras Leukaemia Research Institute, IJC Building, Campus ICO-Germans Trias i Pujol, Ctra de Can Ruti, 08916 Barcelona, Spain.
Cells. 2020 Feb 24;9(2):523. doi: 10.3390/cells9020523.
The transcription factor MYC is transiently expressed during B lymphocyte development, and its correct modulation is essential in defined developmental transitions. Although temporary downregulation of MYC is essential at specific points, basal levels of expression are maintained, and its protein levels are not completely silenced until the B cell becomes fully differentiated into a plasma cell or a memory B cell. MYC has been described as a proto-oncogene that is closely involved in many cancers, including leukemia and lymphoma. Aberrant expression of MYC protein in these hematological malignancies results in an uncontrolled rate of proliferation and, thereby, a blockade of the differentiation process. MYC is not activated by mutations in the coding sequence, and, as reviewed here, its overexpression in leukemia and lymphoma is mainly caused by gene amplification, chromosomal translocations, and aberrant regulation of its transcription. This review provides a thorough overview of the role of MYC in the developmental steps of B cells, and of how it performs its essential function in an oncogenic context, highlighting the importance of appropriate MYC regulation circuitry.
转录因子 MYC 在 B 淋巴细胞发育过程中短暂表达，其正确的调节在特定的发育转变中至关重要。尽管在特定的时间点需要暂时下调 MYC，但它的基础表达水平得以维持，并且直到 B 细胞完全分化为浆细胞或记忆 B 细胞，其蛋白水平才会完全沉默。MYC 被描述为一种原癌基因，与包括白血病和淋巴瘤在内的许多癌症密切相关。在这些血液系统恶性肿瘤中，MYC 蛋白的异常表达导致不受控制的增殖速率，从而阻断分化过程。MYC 不是由编码序列中的突变激活的，正如这里所综述的，白血病和淋巴瘤中的过表达主要是由于基因扩增、染色体易位和其转录的异常调节所致。这篇综述全面概述了 MYC 在 B 细胞发育步骤中的作用，以及它在致癌环境中如何发挥其重要功能，突出了适当的 MYC 调节回路的重要性。
