Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.
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)....
| Päätekijät: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Aineistotyyppi: | Journal article |
| Kieli: | English |
| Julkaistu: |
2011
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| _version_ | 1826289563245477888 |
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| author | Malcovati, L Papaemmanuil, E Bowen, D Boultwood, J Della Porta, MG Pascutto, C Travaglino, E Groves, M Godfrey, A Ambaglio, I Gallì, A Vià, D Conte, S Tauro, S Keenan, N Hyslop, A Hinton, J Mudie, L Wainscoat, J Futreal, P Stratton, MR Campbell, P Hellström-Lindberg, E Cazzola, M |
| author_facet | Malcovati, L Papaemmanuil, E Bowen, D Boultwood, J Della Porta, MG Pascutto, C Travaglino, E Groves, M Godfrey, A Ambaglio, I Gallì, A Vià, D Conte, S Tauro, S Keenan, N Hyslop, A Hinton, J Mudie, L Wainscoat, J Futreal, P Stratton, MR Campbell, P Hellström-Lindberg, E Cazzola, M |
| author_sort | Malcovati, L |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T02:30:47Z |
| format | Journal article |
| id | oxford-uuid:a72a3e2b-d21e-4a2a-9178-32cd67a44ef3 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:30:47Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:a72a3e2b-d21e-4a2a-9178-32cd67a44ef32022-03-27T02:52:41ZClinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a72a3e2b-d21e-4a2a-9178-32cd67a44ef3EnglishSymplectic Elements at Oxford2011Malcovati, LPapaemmanuil, EBowen, DBoultwood, JDella Porta, MGPascutto, CTravaglino, EGroves, MGodfrey, AAmbaglio, IGallì, AVià, DConte, STauro, SKeenan, NHyslop, AHinton, JMudie, LWainscoat, JFutreal, PStratton, MRCampbell, PHellström-Lindberg, ECazzola, MIn 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. |
| spellingShingle | Malcovati, L Papaemmanuil, E Bowen, D Boultwood, J Della Porta, MG Pascutto, C Travaglino, E Groves, M Godfrey, A Ambaglio, I Gallì, A Vià, D Conte, S Tauro, S Keenan, N Hyslop, A Hinton, J Mudie, L Wainscoat, J Futreal, P Stratton, MR Campbell, P Hellström-Lindberg, E Cazzola, M Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title | Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title_full | Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title_fullStr | Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title_full_unstemmed | Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title_short | Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. |
| title_sort | clinical significance of sf3b1 mutations in myelodysplastic syndromes and myelodysplastic myeloproliferative neoplasms |
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