SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts

High frequencies of SF3B1 and JAK2 mutations in refractory anemia with ring sideroblasts associated with marked thrombocytosis strengthen the assignment to the category of myelodysplastic/myeloproliferative neoplasms

“…JAK2V617F was also very frequent (36 of 47, 76.6%). Twenty-five of 36 (69.4%) revealed a mutation load of 10-50%, 6 4 This is mainly related to the high frequency of JAK2V617F (76.6%) in our RARS-T cohort, rarely seen in other studies (31-100%) in 3 to 23 analyzed patients. 8 A very large recent multicenter study with 175 RARS-T patients analyzed for JAK2V617F reported a frequency of 42.9%.…”

“…1 Remarkably, mutations in SF3B1 (splicing factor 3b, subunit 1) were associated with the morphological feature of ring sideroblasts 1-3 and were also found in refractory anemia with ring sideroblasts and marked thrombocytosis (RARS-T). 2,[4][5][6] This malignancy has been assigned as a provisional entity in the chapter "Myelodyplastic/myeloproliferative neoplasms, unclassifiable" of the WHO classification. 7 Patients have anemia, clinical and morphological features of myelodysplastic syndromes (MDS), but also show marked thrombocytosis associated with abnormal megakaryocytes resembling BCR-ABL1 negative myeloproliferative neoplasms (MPN).…”

SF3B1 mutations in primary myelofibrosis: clinical, histopathology and genetic correlates among 155 patients

“…1 These mutations were mutually exclusive and their common functional consequence is believed to involve global abnormalities in RNA splicing, resulting in reduced cell proliferation and increased apoptosis. 1 SF3B1 (located on chromosome 2q33.1) mutations in MDS-RS have also been reported by Papaemmanuil et al 2 and Visconte et al 3 At the time of this writing, details regarding the former study 2 were not available, whereas in the latter study 3 heterozygous SF3B1 mutations were reported in 9 (64%) of 14 patients with RARS, 13 (72%) of 18 patients with RARS and marked thrombocytosis (RARS-T), and none of 24 patients with MDS/MPN without RS. 3 The most common SF3B1 mutation reported by Visconte et al 3 was SF3B1K700E (64%); other mutations described by these authors involved K666 (n ¼ 3), R625 (n ¼ 2), E622 (n ¼ 1), H662 (n ¼ 1) and del699-700QK (n ¼ 1).…”

Clinical implications of U2AF1 mutation in patients with myelodysplastic syndrome and its stability during disease progression

“…It is estimated that >90% of human genes undergo alternative splicing and translate into various protein isoforms for different functions, so this splicing process is important for gene expression diversity [12,13]. The clinical implications of mutations involving some of these splicing machinery genes, like SRSF2 [8,11,[14][15][16][17][18] and SF3B1 [8,9,11,14,[19][20][21][22], in MDS patients have been explored. U2AF1 (synonym U2AF35), another splicing machinery gene frequently mutated in MDS [8,10,15,16], belongs to the splicing factor SR family genes and encodes the small subunit of U2 auxiliary factor complex required for the binding of U2 snRNP to the pre-mRNA branch site [23,24].…”