The clinical impact of IKZF1 mutation in acute myeloid leukemia

The genetic heterogeneity generates great challenges in the understanding and treating acute myeloid leukemia (AML), while the knowledge about IKZF1 mutation in AML was extremely limited. Previously, we described the distribution pattern of IKZF1 mutation in AML, but its clinical impact remained undefined due to limited cases. Herein, we devoted to answer this question in one relatively large cohort. Among 530 newly diagnosed AML patients, we identified 28 IKZF1 mutations in 22 patients (22/530, 4.15%). IKZF1-mutated patients presented one young median morbid age (P=0.027) and the high frequency of mixed lineage leukemia involvement (P=0.012). In AML, IKZF1 mutation showed significant co-occurrences with CEBPA (P<0.001), SF3B1 (P=0.001), or CSF3R (P=0.008) mutation. Though IKZF1-mutated AML was more classified into the intermediate-risky group (P=0.005), it showed one inferior complete remission rate (P=0.041). Furthermore, AML with high variant allele frequency of IKZF1 mutation showed one relatively shorter overall survival duration (P=0.047), and it was one independent factor for the increased risk of death (hazard ratio, 3.14; 95% CI, 1.27-7.75; P=0.013). In subgroup analysis, our results showed that IKZF1 mutation conferred one poor therapeutic response and prognosis for SF3B1-mutated AML (P=0.002). Therefore, IKZF1 mutation exhibited one unique distribution mode and essential prognostic role in AML.