骨髓增生异常综合征DNA甲基化研究进展
丁雪;刘杰;王博;郑舒扬;李丹红;
摘要(Abstract):
骨髓增生异常综合征(MDS)是一种发病机制仍不十分明确的骨髓造血干细胞异质性克隆性疾病,以一系或多系血细胞病态造血为特点,并具有高度向急性髓系白血病(AML)转化的风险,其转白率约30%。随着高通量基因芯片技术的出现,大量研究表明表观遗传学的改变(如DNA甲基化、组蛋白修饰等)参与多种恶性肿瘤的发生、发展。这一观点在MDS的发病机制中也得到了体现,而DNA甲基化作为其常见且最为重要的修饰方式之一,在MDS中占有十分重要地位。本文主要针对MDS疾病中DNA甲基化研究进展进行综述。
关键词(KeyWords): 骨髓增生异常综合征(MDS);DNA甲基化;DNMT3A;TET2;IDH
基金项目(Foundation):
作者(Authors): 丁雪;刘杰;王博;郑舒扬;李丹红;
DOI: 10.13799/j.cnki.mdjyxyxb.2019.04.037
参考文献(References):
- [1] RIVARD G E,MOMPARLER P L,DEMERS J,et al.Phase I study on 5-aza-2'-deoxycytidine in children with acute leukemia[J].Leuk Res,1981,5(6):453-462.
- [2] ISSA J P.The myelodysplastic syndrome as a prototypical epigenetic disease[J].Blood,2013,121(119):3811-3817.
- [3] VISCONTE V,TIU R V,ROGERS H J.Pathogenesis of myelodysplastic syndromes:an overview of molecular and non‐molecular aspects of the disease[J].Blood Res,2014(49):216-227.
- [4] 肖枭,王艳林,黄利鸣.DNA甲基转移酶与肿瘤关系的研究进展[J].生命科学,2019(1):87-92.
- [5] GOLL M G,KIRPEKAR F,MAGGEIT K A,et al.Methylation of tRNAAsp by the DNA methyltransferase homolog DNMT2[J].Science,2006(311):395-398.
- [6] NEBBIOSO A,BENEDETTI R,CONTE M,et al.Genetic mutations in epigenetic modifiers as therapeutic targets in acute myeloid leukemia[J].Expert Opin Ther Targets,2015(19):1187-1202.
- [7] TAHILIANI M,KOH K P,SHEN Y,et al.conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1[J].Science,2009,324(5929):930-935.
- [8] SMITH A E,MOHAMEDALI A M,KULASEKARARA J A,et al.Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins,but indicates no definite prognostic value[J].Blood,2010(116):3923-3932.
- [9] SHALLIS R M,AHMAD R,ZEIDAN A M,et al.Thegeneticandmolecularpathogenesisof myelodysplastic syndromes[J].Eur J Haematol,2018,101(3):260-271.
- [10] CADET J,WAGNER J R.Tet enzymatic oxidation of 5-methylcytosine,5-hydroxymethylcytosine and 5-formylctosine[J].Mutat Res Genet Toxicol Environ Mutagen,2014(6):764-765.
- [11] LIN C C,HOU H A,CHOU W C,et al.IDH mutations are closely associated with mutations ofDNMT3A,ASXL1 and SRSF2 in patients with myelodysplastic syndromes and are stable during disease evolution[J].Am J Hematol,2014(89):137-144.
- [12] WANG N,WANG F,SHAN N,et al.IDH1 Mutation is an independent inferior prognostic indicator for Patients with Myelodysplastic Syndromes[J].Acta Haemetol,2017,138(3):143-151.
- [13] LOSMAN J A,LOOPER R E,KOIVUNEN P,et al.(R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible[J].Science,2013(339):1621-1625.
- [14] PONNALURI V K,MACIEJEWSKI J P,MUKHERJI M.A mechanistic overview of TET-mediated 5-methylcytosine oxidation[J].Biochem Biophys Res Commun,2013(436):115-120.
- [15] LIN M E,HOU H A,TSAI C H,et al.Dynamics of DNMT3A mutation and prognostic relevance in patients with primary myelodysplastic syndrome[J].Clin Epigenetics,2018(10):42.
- [16] LIN J,YAO D M,QIAN J,et al.Recurrent DNMT3A R882 mutations in Chinese patients with acute myeloid leukemia and myelodysplastic syndrome[J].PLoS One,2011(6):e26906.
- [17] DELHOMMEAU F,DUPONT S,DELLA V V,et al.Mutation in TET2 in myeloid cancers[J].N Engl J Med,2009,360(20):2289-2301.
- [18] JONGEN L M,GROB T,HANEKAMP D,et al.Molecular Minimal Residual Disease in Acute Myeloid Leukemia[J].N Engl J Med,2018,378(13):1189-1199.
- [19] LASHO T L,MUDIRDDY M,FINKE C M,et al.Targeted next-generation sequencing in blast phase myeloproliferative neoplasms[J].Blood Adv,2018,2(4):370-380.
- [20] LIN Y,LIN Z,CHENG K,et al.Prognostic role of TET2 deficiency in myelodysplastic syndromes:A meta-analysis[J].Oncotarget,2017,8(26):43295-43305.
- [21] ABBA S S,LUGTHART S,KAVELAARS F G,et al.Acquired mutations in the genes encoding IDH1 and IDH2 both are recurrent aberrations in acute myeloid leukemia:prevalence and prognostic value[J].Blood,2010(116):2122-2126.
- [22] TEFFERI A,LASHO T L,ABDEL W O,et al.IDH1 and IDH2 mutation studies in 1,473 patients with chronic-,fibrotic-or blast-phase essential thrombocythemia,polycythemia vera or myelofibrosis[J].Leukemia,2010(24):1302-1309.
- [23] JIN J,HU C,YU M,et al.Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes:a retrospective cohort study and meta-analysis[J].PLoS One,2014(9):100206.
- [24] SHAHRABI S,KHOSRAVI A,SHAHJAHARI M,et al.Genetics and Epigenetics of Myelodysplastic Syndromes and Response to Drug Therapy:New Insights[J].Oncol Rev,2016,10(2):311.