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SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts.
Malcovati, Luca; Karimi, Mohsen; Papaemmanuil, Elli; Ambaglio, Ilaria; Jädersten, Martin; Jansson, Monika; Elena, Chiara; Gallì, Anna; Walldin, Gunilla; Della Porta, Matteo G; Raaschou-Jensen, Klas; Travaglino, Erica; Kallenbach, Klaus; Pietra, Daniela; Ljungström, Viktor; Conte, Simona; Boveri, Emanuela; Invernizzi, Rosangela; Rosenquist, Richard; Campbell, Peter J; Cazzola, Mario; Hellström Lindberg, Eva.
Afiliación
  • Malcovati L; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Karimi M; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
  • Papaemmanuil E; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom;
  • Ambaglio I; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine, University of Pavia, Pavia, Italy;
  • Jädersten M; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
  • Jansson M; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
  • Elena C; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Gallì A; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Walldin G; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
  • Della Porta MG; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Internal Medicine, University of Pavia, Pavia, Italy;
  • Raaschou-Jensen K; Department of Hematology and.
  • Travaglino E; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Kallenbach K; Department of Pathology, Copenhagen University Hospital, Copenhagen, Denmark;
  • Pietra D; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Ljungström V; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;
  • Conte S; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
  • Boveri E; Department of Pathology, and.
  • Invernizzi R; Department of Internal Medicine, University of Pavia, Pavia, Italy; Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Rosenquist R; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;
  • Campbell PJ; Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, United Kingdom;
  • Cazzola M; Department of Molecular Medicine, University of Pavia, Pavia, Italy; Department of Hematology Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy;
  • Hellström Lindberg E; Center for Hematology and Regenerative Medicine, Karolinska University Hospital, Stockholm, Sweden;
Blood ; 126(2): 233-41, 2015 Jul 09.
Article en En | MEDLINE | ID: mdl-25957392
Refractory anemia with ring sideroblasts (RARS) is a myelodysplastic syndrome (MDS) characterized by isolated erythroid dysplasia and 15% or more bone marrow ring sideroblasts. Ring sideroblasts are found also in other MDS subtypes, such as refractory cytopenia with multilineage dysplasia and ring sideroblasts (RCMD-RS). A high prevalence of somatic mutations of SF3B1 was reported in these conditions. To identify mutation patterns that affect disease phenotype and clinical outcome, we performed a comprehensive mutation analysis in 293 patients with myeloid neoplasm and 1% or more ring sideroblasts. SF3B1 mutations were detected in 129 of 159 cases (81%) of RARS or RCMD-RS. Among other patients with ring sideroblasts, lower prevalence of SF3B1 mutations and higher prevalence of mutations in other splicing factor genes were observed (P < .001). In multivariable analyses, patients with SF3B1 mutations showed significantly better overall survival (hazard ratio [HR], .37; P = .003) and lower cumulative incidence of disease progression (HR = 0.31; P = .018) compared with SF3B1-unmutated cases. The independent prognostic value of SF3B1 mutation was retained in MDS without excess blasts, as well as in sideroblastic categories (RARS and RCMD-RS). Among SF3B1-mutated patients, coexisting mutations in DNA methylation genes were associated with multilineage dysplasia (P = .015) but had no effect on clinical outcome. TP53 mutations were frequently detected in patients without SF3B1 mutation, and were associated with poor outcome. Thus, SF3B1 mutation identifies a distinct MDS subtype that is unlikely to develop detrimental subclonal mutations and is characterized by indolent clinical course and favorable outcome.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Síndromes Mielodisplásicos / Ribonucleoproteína Nuclear Pequeña U2 / Anemia Sideroblástica / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfoproteínas / Síndromes Mielodisplásicos / Ribonucleoproteína Nuclear Pequeña U2 / Anemia Sideroblástica / Mutación Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Blood Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos