Companion gene mutations and their clinical significance in AML with double or single mutant CEBPA

We report the co-mutations in AML with CEBPAsm or CEBPAdm and their clinical features in a large cohort (n = 302) of CEBPAmut AML patients.We retrospectively sequenced 112 genes in 302 patients with CEBPAmut using NGS, and studied the spectrum and clinical impact of co-mutations in CEBPAdm and CEBPAsm.① The average number of mutations in CEBPAsm and CEBPAdm AML was comparable, but not significant (P = 0.17). ② CEBPAdm patients exhibited more mutations in CSF3R (P = 0.037), GATA2 (P = 0.022), and WT1 (P = 0.046). In contrast, CEBPAsm patients more frequently harbored mutations in NPM1 (P = 0.000), FLT3-ITD (P = 0.025) and NOTCH2 (P = 0.043), as well as mutations in signaling pathways and spliceosomes (P = 0.064, P = 0.027, respectively). ③ Patients with CEBPAsm/TET2mut or CEBPAsm /GATA2mut had higher platelet counts (both P = 0.011), while patients with CEBPAdm /TET2mut had significantly higher hemoglobin levels (P = 0.009). The CR rate of patients with FLT3-ITD mutations was significantly lower in the CEBPAsm group than the CEBPAdm group (P = 0.028).CEBPAsm and CEBPAdm AML are each associated with their own complex co-mutation cluster. Some co-mutations influence the clinical features and CR rate differently in patients with different CEBPA mutational status.