Blood Journal
Leading the way in experimental and clinical research in hematology

Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms

  1. Luca Malcovati1,*,
  2. Elli Papaemmanuil2,*,
  3. David T. Bowen3,
  4. Jacqueline Boultwood4,
  5. Matteo G. Della Porta1,
  6. Cristiana Pascutto1,
  7. Erica Travaglino1,
  8. Michael J. Groves5,
  9. Anna L. Godfrey6,
  10. Ilaria Ambaglio1,
  11. Anna Gallì1,
  12. Matteo C. Da Vià1,
  13. Simona Conte7,
  14. Sudhir Tauro5,
  15. Norene Keenan5,
  16. Ann Hyslop5,
  17. Jonathan Hinton2,
  18. Laura J. Mudie2,
  19. James S. Wainscoat4,
  20. P. Andrew Futreal2,
  21. Michael R. Stratton2,
  22. Peter J. Campbell2,
  23. Eva Hellström-Lindberg7,
  24. Mario Cazzola1, and
  25. on behalf of the 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
  1. 1Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and University of Pavia, Pavia, Italy;
  2. 2Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom;
  3. 3Department of Hematology, St James's Institute of Oncology, Leeds, United Kingdom;
  4. 4Leukaemia & Lymphoma Research Molecular Hematology Unit, John Radcliffe Hospital, Oxford, United Kingdom;
  5. 5Department of Hematology, Ninewells Hospital, Dundee, United Kingdom;
  6. 6Department of Hematology, University of Cambridge, United Kingdom; and
  7. 7Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden


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.

  • Submitted September 2, 2011.
  • Accepted October 6, 2011.
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