title: Age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis.
abstract: Refractory anaemia with ring sideroblasts (RARS) and marked thrombocytosis (RARS-T) is a provisional entity in the World Health Organisation 2008 classification and has previously been shown to have a high proportion of JAK2(V617F) (Janus Kinase 2) and SF3B1 (Splicing Factor 3B subunit 1) mutations. The purpose of the present study was to analyse the frequency of SF3B1 mutations in a large cohort of 111 patients with RARS-T and 33 patients with RARS and to explore the prognostic impact of SF3B1 mutational status on RARS-T. The frequency of SF3B1 mutations in RARS-T (96/111, 86.5%) and RARS (28/33, 84.8%) was similar. In RARS-T, median survival was better in SF3B1-mutated patients than in SF3B1-non-mutated patients (6.9 and 3.3 years, respectively, P=0.003). RARS can be differentiated from RARS-T by the frequency of JAK2(V617F) (0% vs 48.6%). In RARS-T patients, SF3B1 (P=0.021) and JAK2 mutations (P=0.016) were independent factors for a better prognosis. Altogether, our results confirm that RARS-T is an independent entity that should be recognised by the next World Health Organisation classification. The assessment of SF3B1 mutations is of prognostic interest in RARS-T patients. Younger age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in RARS-T.
authors.affiliation: Haematology Laboratory, University Hospital, Nancy, France.
authors.forename: J
authors.initials: J
authors.lastname: Broséus
authors.forename: T
authors.initials: T
authors.lastname: Alpermann
authors.forename: M
authors.initials: M
authors.lastname: Wulfert
authors.forename: L
authors.initials: L
authors.lastname: Florensa Brichs
authors.forename: S
authors.initials: S
authors.lastname: Jeromin
authors.forename: E
authors.initials: E
authors.lastname: Lippert
authors.forename: M
authors.initials: M
authors.lastname: Rozman
authors.forename: F
authors.initials: F
authors.lastname: Lifermann
authors.forename: V
authors.initials: V
authors.lastname: Grossmann
authors.forename: T
authors.initials: T
authors.lastname: Haferlach
authors.forename: U
authors.initials: U
authors.lastname: Germing
authors.forename: E
authors.initials: E
authors.lastname: Luño
authors.forename: F
authors.initials: F
authors.lastname: Girodon
authors.forename: S
authors.initials: S
authors.lastname: Schnittger
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000753:Anemia, Refractory / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D000756:Anemia, Sideroblastic / Q000150:complications; D002874:Chromosome Mapping; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D059785:Karyotype; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010750:Phosphoproteins / Q000235:genetics*; D011379:Prognosis; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics*; D013922:Thrombocytosis / Q000150:complications; D055815:Young Adult
chemical_list: D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; D053614:Janus Kinase 2