Brunetti Lorenzo, Gundry Michael C, Goodell Margaret A
Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, Texas 77030.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030.
Cold Spring Harb Perspect Med. 2017 Feb 1;7(2):a030320. doi: 10.1101/cshperspect.a030320.
DNA methylation is an epigenetic process involved in development, aging, and cancer. Although the advent of new molecular techniques has enhanced our knowledge of how DNA methylation alters chromatin and subsequently affects gene expression, a direct link between epigenetic marks and tumorigenesis has not been established. DNMT3A is a de novo DNA methyltransferase that has recently gained relevance because of its frequent mutation in a large variety of immature and mature hematologic neoplasms. DNMT3A mutations are early events during cancer development and seem to confer poor prognosis to acute myeloid leukemia (AML) patients making this gene an attractive target for new therapies. Here, we discuss the biology of DNMT3A and its role in controlling hematopoietic stem cell fate decisions. In addition, we review how mutant DNMT3A may contribute to leukemogenesis and the clinical relevance of DNMT3A mutations in hematologic cancers.
DNA甲基化是一种参与发育、衰老和癌症的表观遗传过程。尽管新分子技术的出现增进了我们对DNA甲基化如何改变染色质并随后影响基因表达的了解,但尚未建立表观遗传标记与肿瘤发生之间的直接联系。DNMT3A是一种从头DNA甲基转移酶,由于其在多种未成熟和成熟血液肿瘤中频繁发生突变,最近受到了关注。DNMT3A突变是癌症发展过程中的早期事件,似乎会使急性髓性白血病(AML)患者的预后不良,这使得该基因成为新疗法的一个有吸引力的靶点。在这里,我们讨论DNMT3A的生物学特性及其在控制造血干细胞命运决定中的作用。此外,我们回顾了突变型DNMT3A如何促进白血病发生以及DNMT3A突变在血液系统癌症中的临床相关性。