SF3B1 deficiency impairs human erythropoiesis via activation of p53 pathway: implications for understanding of ineffective erythropoiesis in MDS.

Huang Y, Hale J, Wang Y, Li W, Zhang S, Zhang J, Zhao H, Guo X, Liu J, Yan H, Yazdanbakhsh K, Huang G, Hillyer CD, Mohandas N, Chen L, Sun L, An X
J Hematol Oncol 11 19 02/12/2018

Abstract

BACKGROUND: SF3B1 is a core component of splicing machinery. Mutations in SF3B1 are frequently found in myelodysplastic syndromes (MDS), particularly in patients with refractory anemia with ringed sideroblasts (RARS), characterized by isolated anemia. SF3B1 mutations have been implicated in the pathophysiology of RARS; however, the physiological function of SF3B1 in erythropoiesis remains unknown.

METHODS: shRNA-mediated approach was used to knockdown SF3B1 in human CD34

RESULTS: We document that SF3B1 knockdown in human CD34

CONCLUSIONS: These findings enabled us to identify novel roles for SF3B1 in human erythropoiesis and provided new insights into its role in regulating normal erythropoiesis. Furthermore, these findings have implications for improved understanding of ineffective erythropoiesis in MDS patients with SF3B1 mutations.

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