Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.
Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.
复制标题
DOI：
10.1182/blood-2011-09-377275
复制
发表时间：
2011-12-08
期刊：
影响因子：
20.3
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
中科院分区：
文献类型：
--
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
在之前的研究中，我们在骨髓增生异常综合征(MDS)患者中发现了SF3B1的体细胞突变，SF3B1是编码RNA剪接机制的核心组件的基因。在这里，我们定义了这些突变在MDS和骨髓增生异常/骨髓增生性肿瘤(MDS/MPN)中的临床意义。应用大规模平行焦磷酸测序技术对MDS、MDS/MPN或由MDS演变而来的急性髓系白血病(AML)患者的SF3B1基因编码外显子进行筛查。533例MDS患者中有150例(28.1%)存在SF3B1基因突变，83例MDS/MPN患者中有16例(19.3%)发生SF3B1基因突变，38例AML患者中有2例(5.3%)发生SF3B1基因突变。SF3B1突变与环状铁母细胞的存在显著相关(P<；.001)，突变等位基因与其比例显著相关(P=.002)。突变基因对环状铁粒母细胞的阳性预测值为97.7%(95%可信区间，93.5%-99.5%)。在包括已确定的危险因素的多变量分析中，发现SF3B1突变与较好的总体生存率(风险比=0.15，P=0.025)和较低的演变为AML的风险(风险比=0.33，P=0.049)独立相关。在MDS和MDS/MPN中，SF3B1突变和疾病表型与环状铁母细胞密切相关，这与因果关系是一致的。此外，SF3B1突变是良好临床结局的独立预测因子，将其纳入分层系统可能会改善MDS的风险评估。
In a previous study, we identified somatic mutations of SF3B1, a gene encoding a core component of RNA splicing machinery, in patients with myelodysplastic syndrome (MDS). Here, we define the clinical significance of these mutations in MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). The coding exons of SF3B1 were screened using massively parallel pyrosequencing in patients with MDS, MDS/MPN, or acute myeloid leukemia (AML) evolving from MDS. Somatic mutations of SF3B1 were found in 150 of 533 (28.1%) patients with MDS, 16 of 83 (19.3%) with MDS/MPN, and 2 of 38 (5.3%) with AML. There was a significant association of SF3B1 mutations with the presence of ring sideroblasts (P < .001) and of mutant allele burden with their proportion (P = .002). The mutant gene had a positive predictive value for ring sideroblasts of 97.7% (95% confidence interval, 93.5%-99.5%). In multivariate analysis including established risk factors, SF3B1 mutations were found to be independently associated with better overall survival (hazard ratio = 0.15, P = .025) and lower risk of evolution into AML (hazard ratio = 0.33, P = .049). The close association between SF3B1 mutations and disease phenotype with ring sideroblasts across MDS and MDS/MPN is consistent with a causal relationship. Furthermore, SF3B1 mutations are independent predictors of favorable clinical outcome, and their incorporation into stratification systems might improve risk assessment in MDS.
登录
查看更多内容
影响因子：
30.8
作者：
Langemeijer, Saskia M. C.;Kuiper, Roland P.;Jansen, Joop H.
通讯作者：
Jansen, Joop H.
影响因子：
6.5
作者：
CAZZOLA, M;BAROSI, G;ASCARI, E
通讯作者：
ASCARI, E
DOI：
10.3324/haematol.13405
发表时间：
2008-11-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Mufti, Ghulam J.;Bennett, John M.;Yoshimi, Ayami
通讯作者：
Yoshimi, Ayami
影响因子：
20.3
作者：
Greenberg, P;Cox, C;Bennett, J
通讯作者：
Bennett, J
影响因子：
64.8
作者：
Ebert, Benjamin L.;Pretz, Jennifer;Bosco, Jocelyn;Chang, Cindy Y.;Tamayo, Pablo;Galili, Naomi;Raza, Azra;Root, David E.;Attar, Eyal;Ellis, Steven R.;Golub, Todd R.
通讯作者：
Golub, Todd R.