The significance of spliceosome mutations in chronic lymphocytic leukemia.
The significance of spliceosome mutations in chronic lymphocytic leukemia.
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DOI：
10.3109/10428194.2012.742528
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发表时间：
2013-07
影响因子：
2.6
通讯作者：
Estrov Z
中科院分区：
文献类型：
--
作者：
Rozovski U;Keating M;Estrov Z
通过选择性剪接产生的细胞蛋白质为肿瘤细胞提供存活优势和/或促进肿瘤细胞增殖。前体mRNA通过由小核RNA（snRNA）和蛋白质亚基组成的大复合体剪接。在40 - 80%的骨髓增生异常综合征（MDS）患者中检测到剪接体基因突变，特别是在环形铁粒幼细胞中。最近，两项大型全基因组测序研究在约10%的慢性淋巴细胞白血病（CLL）患者中发现了剪接体基因SF 3B 1的突变。受这些发现的启发，我们进行了途径富集分析，发现与MDS不同，CLL中剪接体突变几乎仅存在于SF 3B 1中。具有SF 3B 1基因突变的CLL患者的特征是无进展生存期短和10年生存率低。此外，SF 3B 1突变的频率在化疗治疗的CLL患者中显著高于未治疗的CLL患者，表明化疗诱导SF 3B 1基因突变或选择突变细胞群体。SF 3B 1基因突变是否在白血病发生中起作用，无论是因为剪接改变还是其他剪接无关的功能，如先前在SF 3B 1 +/-小鼠中报道的Homobox（Hox）基因的异位表达，仍有待确定。
Cellular proteins produced via alternative splicing, provide neoplastic cells with survival advantage and/or promote neoplastic cell proliferation. Pre-mRNA is spliced by the spliceosome consisting of large complexes of small nuclear RNA (snRNA) and protein subunits. Spliceosome gene mutations were detected in 40 – 80% of patients with myelodysplastic syndrome (MDS), particularly in those with ringed sideroblasts. Recently, two large whole genome sequencing studies identified mutations in the spliceosome gene SF3B1 in approximately 10% of patients with chronic lymphocytic leukemia (CLL). Intrigued by these findings, we performed a pathway enrichment analysis and found that unlike in MDS, in CLL spliceosome mutations exist almost exclusively in SF3B1. CLL patients with an SF3B1 gene mutation are characterized by a short progression-free survival and a low 10 year-survival rate. Furthermore, the frequency of SF3B1 mutations is significantly higher in chemotherapy treated than in untreated patients with CLL, suggesting that chemotherapy induces SF3B1 gene mutations or selects a population of mutated cells. Whether SF3B1 gene mutations have a role in leukemogenesis, either because of altered splicing or other splicing-unrelated functions such as ectopic expression of Homobox (Hox) genes previously reported in SF3B1+/- mice, remains to be determined.
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影响因子：
64.8
作者：
Ellis, Matthew J.;Ding, Li;Shen, Dong;Luo, Jingqin;Suman, Vera J.;Wallis, John W.;Van Tine, Brian A.;Hoog, Jeremy;Goiffon, Reece J.;Goldstein, Theodore C.;Ng, Sam;Lin, Li;Crowder, Robert;Snider, Jacqueline;Ballman, Karla;Weber, Jason;Chen, Ken;Koboldt, Daniel C.;Kandoth, Cyriac;Schierding, William S.;McMichael, Joshua F.;Miller, Christopher A.;Lu, Charles;Harris, Christopher C.;McLellan, Michael D.;Wendl, Michael C.;DeSchryver, Katherine;Allred, D. Craig;Esserman, Laura;Unzeitig, Gary;Margenthaler, Julie;Babiera, G. V.;Marcom, P. Kelly;Guenther, J. M.;Leitch, Marilyn;Hunt, Kelly;Olson, John;Tao, Yu;Maher, Christopher A.;Fulton, Lucinda L.;Fulton, Robert S.;Harrison, Michelle;Oberkfell, Ben;Du, Feiyu;Demeter, Ryan;Vickery, Tammi L.;Elhammali, Adnan;Piwnica-Worms, Helen;McDonald, Sandra;Watson, Mark;Dooling, David J.;Ota, David;Chang, Li-Wei;Bose, Ron;Ley, Timothy J.;Piwnica-Worms, David;Stuart, Joshua M.;Wilson, Richard K.;Mardis, Elaine R.
通讯作者：
Mardis, Elaine R.
DOI：
10.1056/nejmoa1103283
发表时间：
2011-10-13
期刊：
The New England journal of medicine
影响因子：
--
作者：
Papaemmanuil E;Cazzola M;Boultwood J;Malcovati L;Vyas P;Bowen D;Pellagatti A;Wainscoat JS;Hellstrom-Lindberg E;Gambacorti-Passerini C;Godfrey AL;Rapado I;Cvejic A;Rance R;McGee C;Ellis P;Mudie LJ;Stephens PJ;McLaren S;Massie CE;Tarpey PS;Varela I;Nik-Zainal S;Davies HR;Shlien A;Jones D;Raine K;Hinton J;Butler AP;Teague JW;Baxter EJ;Score J;Galli A;Della Porta MG;Travaglino E;Groves M;Tauro S;Munshi NC;Anderson KC;El-Naggar A;Fischer A;Mustonen V;Warren AJ;Cross NC;Green AR;Futreal PA;Stratton MR;Campbell PJ;Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
通讯作者：
Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium
影响因子：
3.7
作者：
Harris DM;Hazan-Haley I;Coombes K;Bueso-Ramos C;Liu J;Liu Z;Li P;Ravoori M;Abruzzo L;Han L;Singh S;Sun M;Kundra V;Kurzrock R;Estrov Z
通讯作者：
Estrov Z
影响因子：
20.3
作者：
Rossi, Davide;Bruscaggin, Alessio;Gaidano, Gianluca
通讯作者：
Gaidano, Gianluca
影响因子：
20.3
作者：
Makishima, Hideki;Visconte, Valeria;Maciejewski, Jaroslaw P.
通讯作者：
Maciejewski, Jaroslaw P.