Prognostic significance of ASXL1 mutations in myelodysplastic syndromes and chronic myelomonocytic leukemia: A meta-analysis.

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.