Impact of splicing factor mutations on clinical features in patients with myelodysplastic syndromes

• Published in: International journal of hematology 2018-12, Vol.108 (6), p.598-606
• Main Authors: Shingai, Naoki, Harada, Yuka, Iizuka, Hiroko, Ogata, Yosuke, Doki, Noriko, Ohashi, Kazuteru, Hagihara, Masao, Komatsu, Norio, Harada, Hironori
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Anemia; Biomarkers; Blood Cell Count; Blood Transfusion; Bone marrow; Bone Marrow - pathology; Classification; Dependence; Disorders; DNA Mutational Analysis; Erythrocyte Indices; Erythrocytes; Female; Genetic Association Studies; Hematology; Humans; Incidence; Kaplan-Meier Estimate; Male; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Mutation; Myelodysplastic syndrome; Myelodysplastic syndromes; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - genetics; Myelodysplastic Syndromes - mortality; Myelodysplastic Syndromes - therapy; Oncology; Original Article; Patients; Phenotypes; Platelets; Prognosis; Proportional Hazards Models; Refractory anemia; RNA Splicing Factors - genetics; Sideroblasts; Splicing factors; Survival; Symptom Assessment; Transfusion
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-018-2551-y

Splicing factor gene mutations are found in 60–70% of patients with myelodysplastic syndromes (MDS). We investigated the effects of splicing factor gene mutations on the diagnosis, patient characteristics, and prognosis of MDS. A total of 106 patients with MDS were included. The percentage of patients with MDS with ring sideroblasts (14.15%) as per the 2017 WHO classification was significantly higher than that of patients with refractory anemia with ring sideroblasts (2.88%) as per the 2008 WHO classification ( P  = 0.005). Splicing factor mutations were detected in 32 patients (13 SF3B1 , 8 U2AF1 , and 11 SRSF2 ), and the mutations were mutually exclusive. Significant differences were observed in the mean corpuscular volume, platelet count, bone marrow myeloid:erythroid ratio, and megakaryocyte count in patients with different mutations. SRSF2 mutations were associated with a high cumulative incidence of red blood cell transfusion dependence, while SF3B1 mutations were associated with a low cumulative incidence of platelet concentrate transfusion dependence. Presence of SF3B1 mutation was a significant univariate predictor of overall survival, but become nonsignificant in the multivariate model. Although many factors also could affect survival, these results suggest that splicing factor mutations contribute to distinct MDS phenotypes, including patient characteristics and clinical courses.