Prognostic significance of SETBP1 mutations in myelodysplastic syndromes, chronic myelomonocytic leukemia, and chronic neutrophilic leukemia: A meta-analysis.

Li-Hong Shou,Yan Zhang,Ying Wu,Qiu Fang,Ju-Ping Fei,Dan Cao,Bao-Lian Xu,Xiao-Hui Dong,Robert K Hills

doi:10.1371/journal.pone.0171608

Abstract

ObjectivesThis meta-analysis investigates the prognostic effect of SET binding protein 1 (SETBP1) mutations in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL).MethodsEligible studies from Pubmed, Embase, and Web of Science were searched from database inception through April 2016. Hazard ratios (HRs) and 95% confidence interval (CI) of overall survival (OS) were pooled to calculate the prognostic significance of SETBP1 mutation in patients.ResultsA total of 12 studies with 2321 patients were included in this meta-analysis; 4 studies for MDS, 5 studies for CMML, and 3 studies for CNL. Pooled results suggested that MDS and CMML patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: HR = 1.808, 95% CI (1.218–2.685), P = 0.001; CMML: HR = 2.223, 95% CI (1.493–3.308), P<0.001). SETBP1 mutations in CNL patients however, showed no significant effect on the overall survival (HR = 1.773, 95% CI (0.877–3.582), P = 0.111). The Begg’s and Egger’s tests did not show significant publication bias in any groups.ConclusionsCurrent evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with CNL.

Highlights

SETBP1, a gene located on chromosome 18q21.1, encodes SET binding protein 1 that binds with SET nuclear oncoprotein to form a heterodimer complex
Pooled results suggested that myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) patients with SETBP1 mutations had a significantly poorer prognosis when compared with patients with wild-type SETBP1 (MDS: Hazard ratios (HRs) = 1.808, 95% confidence interval (CI) (1.218–2.685), P = 0.001; CMML: HR = 2.223, 95% confidence interval (95% CI) (1.493–3.308), P
Current evidence shows that SETBP1 mutation is associated with a poor prognosis in patients with MDS and CMML, but not in patients with chronic neutrophilic leukemia (CNL)

Summary

Introduction

SETBP1, a gene located on chromosome 18q21.1, encodes SET binding protein 1 that binds with SET nuclear oncoprotein to form a heterodimer complex. In vitro studies have suggested that this heterodimer inhibits the activity of protein phosphatase type 2A (PP2A), a tumor suppressor, and increases the rate of cell proliferation [1, 2]. In 2013, exome-sequencing analysis of patients with atypical chronic myeloid leukemia (aCML) identified the presence of missense SETBP1 mutations [2]. Patients who had SETBP1 mutations had poorer prognosis with a higher white blood cell count when compared with patients who had wild-type SETBP1 [2]. These mutations were clustered from residue 858 to 871 located in the highly conserved SKI-homologous domain [3], suggesting a functional alteration in the mutations

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Results

Conclusion