Department of Pediatric Oncology and Hematology, Erasmus MC/Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Leukemia. 2012 Jan;26(1):1-12. doi: 10.1038/leu.2011.151. Epub 2011 Jun 24.
MicroRNAs (miRNAs) are involved in the management of hematopoiesis. As a consequence, miRNA dysregulation causes disruption of the hematopoietic system and leukemia may arise. We here comprehensively discuss miRNAs found discriminative for cytogenetic and molecular subtypes of acute leukemia. These miRNAs are either known miRNAs involved in leukemogenesis with proven tumor suppressor or oncogenic activities or are newly identified by high-throughput sequencing with yet unknown function. Furthermore, forces are outlined that drive aberrant miRNA function, which include genetic abnormalities (for example, deletions, translocations and mutations) and epigenetic aberrations (for example, aberrant DNA methylation or histone modifications). Interestingly, leukemia-silenced miRNAs can be re-expressed upon treatment with de-methylating agents. Targeting miRNA expression may serve a therapeutical role, albeit at present this way of targeted therapy is in its infancy. However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia.
微小 RNA（miRNAs）参与造血的调控。因此，miRNA 失调会导致造血系统紊乱，可能导致白血病的发生。我们在这里全面讨论了在急性白血病的细胞遗传学和分子亚型中具有区分能力的 miRNAs。这些 miRNAs 或者是已知的参与白血病发生的 miRNA，具有已证实的肿瘤抑制或致癌活性，或者是通过高通量测序新鉴定的，其功能尚不清楚。此外，还概述了导致异常 miRNA 功能的因素，包括遗传异常（例如缺失、易位和突变）和表观遗传异常（例如异常的 DNA 甲基化或组蛋白修饰）。有趣的是，白血病沉默的 miRNAs 可以在使用去甲基化剂治疗后重新表达。靶向 miRNA 表达可能具有治疗作用，尽管目前这种靶向治疗还处于起步阶段。然而，关于 miRNA 在白血病中的生物学的新知识可能会使这些 miRNAs 在急性白血病的诊断和治疗中发挥作用。
