Yun Lin1, Yi Zheng1, Ze-Chuan Wang1, Shao-Yuan Wang2. 1. a Union Clinical Medical College, Fujian Medical University , Fuzhou , P.R. China. 2. b Department of Hematology, Fujian Provincial Key Laboratory on Hematology , Fujian Medical University Union Hospital , Fuzhou , P.R. China.
Abstract
OBJECTIVES: Although additional sex comb-like 1 (ASXL1) gene mutations have long been reported in myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML), the prognostic significance has been controversial. Therefore, a meta-analysis to study the impact of ASXL1 mutations on patients with MDS and CMML is useful. METHODS: The identified articles were retrieved from some common databases. We extracted hazard ratios (HRs) for overall survival (OS) and leukemic-free survival (LFS) and P-value of some clinical parameters, which compared AXSL1 mutations to those without from the available studies. Each individual HR and P-value was used to calculate the pooled HR and P-value. RESULTS: Six studies covering 1689 patients were selected for this meta-analysis. The pooled HRs for OS and LFS were 1.45 (95% confidential interval (CI), 1.24-1.70) and 2.20 (95% CI, 1.53-3.17), respectively. When considering CMML patients alone the HR for OS was 1.50 (95% CI, 1.18-1.90). Additionally, ASXL1 mutations were more frequently found in male (P = 0.008), older (P = 0.019), and patients with lower platelets (P = 0.009) or hemoglobin level (P = 0.0015) and associated with other mutations such as EZH2, IDH1/2, RUNX1, and TET2. DISCUSSION: Although our analysis has its limitation, it showed that ASXL1 mutations had significant inferior impact on OS and LFS for French-American-British-defined MDS patients. However, the influence of different types of ASXL1 mutations on patients with MDS still needs illustrating. CONCLUSION: ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.
OBJECTIVES: Although additional sex comb-like 1 (ASXL1) gene mutations have long been reported in myelodysplastic syndromes (MDSs) and chronic myelomonocytic leukemia (CMML), the prognostic significance has been controversial. Therefore, a meta-analysis to study the impact of ASXL1 mutations on patients with MDS and CMML is useful. METHODS: The identified articles were retrieved from some common databases. We extracted hazard ratios (HRs) for overall survival (OS) and leukemic-free survival (LFS) and P-value of some clinical parameters, which compared AXSL1 mutations to those without from the available studies. Each individual HR and P-value was used to calculate the pooled HR and P-value. RESULTS: Six studies covering 1689 patients were selected for this meta-analysis. The pooled HRs for OS and LFS were 1.45 (95% confidential interval (CI), 1.24-1.70) and 2.20 (95% CI, 1.53-3.17), respectively. When considering CMMLpatients alone the HR for OS was 1.50 (95% CI, 1.18-1.90). Additionally, ASXL1 mutations were more frequently found in male (P = 0.008), older (P = 0.019), and patients with lower platelets (P = 0.009) or hemoglobin level (P = 0.0015) and associated with other mutations such as EZH2, IDH1/2, RUNX1, and TET2. DISCUSSION: Although our analysis has its limitation, it showed that ASXL1 mutations had significant inferior impact on OS and LFS for French-American-British-defined MDSpatients. However, the influence of different types of ASXL1 mutations on patients with MDS still needs illustrating. CONCLUSION:ASXL1 mutations were associated with poor prognosis in MDS, which may contribute to risk stratification and prognostic assessment in the disease.
Authors: Peter Valent; Wolfgang Kern; Gregor Hoermann; Jelena D Milosevic Feenstra; Karl Sotlar; Michael Pfeilstöcker; Ulrich Germing; Wolfgang R Sperr; Andreas Reiter; Dominik Wolf; Michel Arock; Torsten Haferlach; Hans-Peter Horny Journal: Int J Mol Sci Date: 2019-02-12 Impact factor: 5.923
Authors: Raphael Itzykson; Pierre Fenaux; David Bowen; Nicholas C P Cross; Jorge Cortes; Theo De Witte; Ulrich Germing; Francesco Onida; Eric Padron; Uwe Platzbecker; Valeria Santini; Guillermo F Sanz; Eric Solary; Arjan Van de Loosdrecht; Luca Malcovati Journal: Hemasphere Date: 2018-11-29