Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center and the Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Adv Exp Med Biol. 2013;792:309-25. doi: 10.1007/978-1-4614-8051-8_14.
B-cell chronic lymphocytic leukemia (CLL) is the most frequent human leukemia and it occurs in two forms, indolent and aggressive. Although clinical features and genetic abnormalities in CLL are well documented, molecular details underlying the disease are still under investigation.MicroRNAs are small noncoding RNAs involved in a variety of cellular processes and expressed in a tissue-specific manner. MicroRNAs have the ability to regulate gene expression. In physiological conditions, microRNAs act as gene expression controllers by targeting the mRNA or inhibiting its translation. Their deregulation can lead to an alteration of the expression level of many genes which can induce the development or promote the progression of tumors.In CLL, microRNAs can function as oncogenes, tumor suppressor genes, and/or can be used as markers for disease onset/progression. For example, in indolent CLL, 13q14 deletions targeting miR-15/16 initiate the disease, while in aggressive CLL miR-181 targets the critical TCL1 oncogene and can also be used as a progression marker.Here we discuss the foremost findings about the role of microRNAs in CLL pathogenesis, and how this knowledge can be used to identify new approaches to treat CLL.
B 细胞慢性淋巴细胞白血病（CLL）是最常见的人类白血病，它有两种形式，惰性和侵袭性。尽管 CLL 的临床特征和遗传异常已有详细记录，但疾病的分子细节仍在研究中。微小 RNA 是参与多种细胞过程的小非编码 RNA，并以组织特异性方式表达。微小 RNA 能够调节基因表达。在生理条件下，微小 RNA 通过靶向 mRNA 或抑制其翻译来作为基因表达控制器。它们的失调可能导致许多基因的表达水平发生改变，从而诱导肿瘤的发生或促进肿瘤的进展。在 CLL 中，微小 RNA 可以作为癌基因、肿瘤抑制基因发挥作用，和/或可用作疾病发生/进展的标志物。例如，在惰性 CLL 中，靶向 miR-15/16 的 13q14 缺失引发疾病，而在侵袭性 CLL 中，miR-181 靶向关键的 TCL1 癌基因，也可用作进展标志物。在这里，我们讨论了微小 RNA 在 CLL 发病机制中的主要作用，以及如何利用这些知识来确定治疗 CLL 的新方法。
