Yang Zhu1, Xiao Li2, Chunkang Chang1, Feng Xu1, Qi He1, Juan Guo1, Ying Tao1, Yizhi Liu1, Li Liu1, Wenhui Shi1. 1. Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. 2. Department of Haematology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China. Electronic address: lixiao3326@163.com.
Abstract
OBJECTIVE: To clarify the possible biological differences and implication of the SF3B1 gene for patients with MDS-RS (myelodysplastic syndromes with ring sideroblasts). METHODS: Sanger sequencing was performed on mutation hotspots of the SF3B1 gene in MDS-RS patients. The differences between the SF3B1 mutated and wild-type subsets, including the ultrastructure of erythroid precursors, iron profile parameters, erythropoiesis-related measurements, as well as clinical features, were analyzed. RESULTS: SF3B1 mutations were detected in 33 out of fifty-two MDS-RS patients (63%). The vast majority of patients with mutations (94%) were categorized in the lower risk group according to the IPSS (International Prognostic Scoring System), in contrast to only fifty-eight percent of the wild-type cases. In addition to the notably higher percentages of erythroblasts and ring sideroblasts in patients with mutations, abundant electron-dense granules in the mitochondria of the erythroid precursors were clearly observed. Moreover, patients with mutations presented both improper iron uptake and distribution (lower serum hepcidin-25 concentration, P=0.028) and enhanced erythropoietic activity (higher soluble transferrin receptor level, P=0.132; higher growth differentiation factor 15 concentration, P<0.001). Finally, MDS-RS patients carrying SF3B1 mutations had a better overall survival (median 38 vs. 18 months, P=0.001) compared to those without mutations. By multivariable analysis, the prognostic significance of the SF3B1 mutation was primarily accounted for by IPSS risk categorization. CONCLUSION: MDS-RS patients carrying SF3B1 mutations harbored a more severe iron overload and corresponding over-erythropoiesis. The better overall survival of SF3B1-mutated MDS-RS patients may be mainly due to the clustering of patients with lower risk disease in this group.
OBJECTIVE: To clarify the possible biological differences and implication of the SF3B1 gene for patients with MDS-RS (myelodysplastic syndromes with ring sideroblasts). METHODS: Sanger sequencing was performed on mutation hotspots of the SF3B1 gene in MDS-RSpatients. The differences between the SF3B1 mutated and wild-type subsets, including the ultrastructure of erythroid precursors, iron profile parameters, erythropoiesis-related measurements, as well as clinical features, were analyzed. RESULTS:SF3B1 mutations were detected in 33 out of fifty-two MDS-RSpatients (63%). The vast majority of patients with mutations (94%) were categorized in the lower risk group according to the IPSS (International Prognostic Scoring System), in contrast to only fifty-eight percent of the wild-type cases. In addition to the notably higher percentages of erythroblasts and ring sideroblasts in patients with mutations, abundant electron-dense granules in the mitochondria of the erythroid precursors were clearly observed. Moreover, patients with mutations presented both improper iron uptake and distribution (lower serum hepcidin-25 concentration, P=0.028) and enhanced erythropoietic activity (higher soluble transferrin receptor level, P=0.132; higher growth differentiation factor 15 concentration, P<0.001). Finally, MDS-RSpatients carrying SF3B1 mutations had a better overall survival (median 38 vs. 18 months, P=0.001) compared to those without mutations. By multivariable analysis, the prognostic significance of the SF3B1 mutation was primarily accounted for by IPSS risk categorization. CONCLUSION:MDS-RSpatients carrying SF3B1 mutations harbored a more severe iron overload and corresponding over-erythropoiesis. The better overall survival of SF3B1-mutated MDS-RSpatients may be mainly due to the clustering of patients with lower risk disease in this group.
Authors: Sarah Parisi; Carlo Finelli; Antonietta Fazio; Alessia De Stefano; Sara Mongiorgi; Stefano Ratti; Alessandra Cappellini; Anna Maria Billi; Lucio Cocco; Matilde Y Follo; Lucia Manzoli Journal: Int J Mol Sci Date: 2021-01-15 Impact factor: 5.923
Authors: Yen K Lieu; Zhaoqi Liu; Abdullah M Ali; Xin Wei; Alex Penson; Jian Zhang; Xiuli An; Raul Rabadan; Azra Raza; James L Manley; Siddhartha Mukherjee Journal: Proc Natl Acad Sci U S A Date: 2022-01-04 Impact factor: 12.779