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 JAK2V617F (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 JAK2V617F (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, JAK2V617F and SF3B1 mutations are the main predicting factors for survival in RARS-T.
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Acknowledgements
We thank the Medical Doctors from the Haematology Department and Laboratory of the University Hospital of Dijon, the Spanish Group of Hematological Cytology (GECH), as well as Philip Bastable for revising the manuscript. EL and FL are grateful to the Tumor Bank of the CHU of Bordeaux. This work was supported by grants from the association ‘Tulipes contre le cancer’ (Châlon s/Saône, Burgundy, France) and from FEHH (Spain) and 2009 SGR 541 (Generalitat de Catalunya).
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SS and TH declare part ownership of the MLL Munich Leukemia Laboratory. TA, SJ and VG are employed by the MLL Munich Leukemia Laboratory. All the other authors declare no conflict of interest.
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Broséus, J., Alpermann, T., Wulfert, M. et al. Age, JAK2V617F and SF3B1 mutations are the main predicting factors for survival in refractory anaemia with ring sideroblasts and marked thrombocytosis. Leukemia 27, 1826–1831 (2013). https://doi.org/10.1038/leu.2013.120
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DOI: https://doi.org/10.1038/leu.2013.120
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