Distinct clinical and biological characteristics of patients with MDS with higher bone marrow plasma S100A8/A9. (A) Scatter plots shows a moderate correlation between ASXL1 VAF and S100A8/A9 levels. (B) Heatmap of correlations among mutations. (C) Clustering 51 ASXL1-mutated patients based on concurrent mutations of STAG2, RUNX1, EZH2, and ZRSR2. (D) Cluster 1 had a trend of higher S100A8/A9 levels than cluster 2. (E) Higher S100A8/A9 conferred inferior LFS and OS of the 215 patients with MDS. (F) Higher S100A8/A9 conferred significantly worse OS in ICC lower-risk group and higher-risk group. Higher-risk: MDS with excess blast and MDS/AML; and lower-risk: others. (G) Higher S100A8/A9 conferred significantly shorter OS in IPSS-R lower-risk (very low, low, and intermediate) group and a trend of worse OS in IPSS-R higher-risk (IPSS-R high and very high) group. (H) Time-dependent ROC curve analyses demonstrate that S100A8/A9 levels can be complementary to IPSS-R, increasing area under curves when incorporated. (I) Patients with higher S100A8/A9 had significantly inferior OS irrespective of their ASXL1 mutation statuses. ROC, receiver operating characteristic.