Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders.
Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders.
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DOI：
10.1038/leu.2012.130
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发表时间：
2012-12
期刊：
影响因子：
11.4
通讯作者：
Tiu, R. V.
中科院分区：
文献类型：
--
作者：
Visconte, V.;Makishima, H.;Maciejewski, J. P.;Tiu, R. V.
在人类中，大多数蛋白质编码转录物都含有内含子，这些内含子通过剪接体进行的 mRNA 剪接而被去除。最近使用全外显子组/基因组技术在骨髓增生异常综合征（MDS）和其他血液疾病中发现了剪接体机制的突变。剪接因子 3 亚基 b1 (SF3b1) 的改变是第一个被描述的剪接体突变，随后立即鉴定出其他剪接因子突变，包括 U2 小核 RNA 辅助因子 1 (U2AF1) 和富含丝氨酸精氨酸剪接因子 2 (SRSF2)。 SF3b1/U2AF1/SRSF2 突变在不同的疾病亚型中以不同的频率发生，每种突变都会导致生存结果的差异。然而，这些剪接体突变在MDS和其他血液恶性肿瘤发病机制中的确切功能后果仍然很大程度上未知，并且需要深入研究。对于 SF3b1，功能突变的获得可能为携带这种分子异常的疾病提供新的靶向疗法，并有可能治愈。本综述旨在全面概述剪接体机制在MDS/血液疾病生物学中的新兴作用，重点关注突变的功能后果、其临床意义以及它们如何影响我们对受这些突变影响的疾病的理解和管理的观点。
In humans, the majority of all protein-coding transcripts contain introns that are removed by mRNA splicing carried out by spliceosomes. Mutations in the spliceosome machinery have recently been identified using whole exome/genome technologies in myelodysplastic syndromes (MDS) and in other hematologic disorders. Alterations in Splicing Factor 3 Subunit b1 (SF3b1) were the first spliceosomal mutations described, immediately followed by identification of other splicing factor mutations, including U2 Small Nuclear RNA Auxillary Factor 1 (U2AF1) and Serine Arginine Rich Splicing Factor 2 (SRSF2). SF3b1/U2AF1/SRSF2 mutations occur at varying frequencies in different disease subtypes, each contributing to differences in survival outcomes. However, the exact functional consequences of these spliceosomal mutations in the pathogenesis of MDS and other hematologic malignancies remain largely unknown and subject to intense investigation. For SF3b1, a gain of function mutation may offer the promise of new targeted therapies for diseases that carry this molecular abnormality that can potentially lead to cure. This review aims to provide a comprehensive overview of the emerging role of the spliceosome machinery in the biology of MDS/hematologic disorders with an emphasis on the functional consequences of mutations, their clinical significance, and perspectives on how they may influence our understanding and management of diseases affected by these mutations.
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影响因子：
3.5
作者：
López-Bigas, N;Audit, B;Guigó, R
通讯作者：
Guigó, R
影响因子：
3.9
作者：
Ducamp, Sarah;Kannengiesser, Caroline;Grandchamp, Bernard
通讯作者：
Grandchamp, Bernard
DOI：
10.1056/nejmoa1005143
发表时间：
2010-12-16
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ley TJ;Ding L;Walter MJ;McLellan MD;Lamprecht T;Larson DE;Kandoth C;Payton JE;Baty J;Welch J;Harris CC;Lichti CF;Townsend RR;Fulton RS;Dooling DJ;Koboldt DC;Schmidt H;Zhang Q;Osborne JR;Lin L;O'Laughlin M;McMichael JF;Delehaunty KD;McGrath SD;Fulton LA;Magrini VJ;Vickery TL;Hundal J;Cook LL;Conyers JJ;Swift GW;Reed JP;Alldredge PA;Wylie T;Walker J;Kalicki J;Watson MA;Heath S;Shannon WD;Varghese N;Nagarajan R;Westervelt P;Tomasson MH;Link DC;Graubert TA;DiPersio JF;Mardis ER;Wilson RK
通讯作者：
Wilson RK
影响因子：
20.3
作者：
Malcovati L;Papaemmanuil E;Bowen DT;Boultwood J;Della Porta MG;Pascutto C;Travaglino E;Groves MJ;Godfrey AL;Ambaglio I;Gallì A;Da Vià MC;Conte S;Tauro S;Keenan N;Hyslop A;Hinton J;Mudie LJ;Wainscoat JS;Futreal PA;Stratton MR;Campbell PJ;Hellström-Lindberg E;Cazzola M;Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium and of the Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative
通讯作者：
Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium and of the Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative
影响因子：
5.7
作者：
Albert BJ;McPherson PA;O'Brien K;Czaicki NL;Destefino V;Osman S;Li M;Day BW;Grabowski PJ;Moore MJ;Vogt A;Koide K
通讯作者：
Koide K