SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts.

Malcovati L, Karimi M, Papaemmanuil E, Ambaglio I, Jädersten M, Jansson M, Elena C, Gallì A, Walldin G, Della Porta MG, Raaschou-Jensen K, Travaglino E, Kallenbach K, Pietra D, Ljungström V, Conte S, Boveri E, Invernizzi R, Rosenquist R, Campbell PJ, Cazzola M, Hellström Lindberg E

Blood 126 (2) 233-241 [2015-07-09; online 2015-05-10]

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.

Clinical Genomics Uppsala

NGI Stockholm (Genomics Applications)

NGI Stockholm (Genomics Production)

National Genomics Infrastructure

PubMed 25957392

DOI 10.1182/blood-2015-03-633537

Crossref 10.1182/blood-2015-03-633537

pii: blood-2015-03-633537
pmc: PMC4528082

Publications 9.5.0