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

Introduction We report the co-mutations in AML with CEBPA sm or CEBPA dm and their clinical features in a large cohort ( n = 302) of CEBPA mut AML patients. Materials and methods We retrospectively sequenced 112 genes in 302 patients with CEBPA mut using NGS, and studied the spectrum and clinical impact of co-mutations in CEBPA dm and CEBPA sm . Results ① The average number of mutations in CEBPA sm and CEBPA dm AML was comparable, but not significant ( P = 0.17). ② CEBPA dm patients exhibited more mutations in CSF3R ( P = 0.037), GATA2 ( P = 0.022), and WT1 ( P = 0.046). In contrast, CEBPA sm 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 CEBPA sm / TET2 mut or CEBPA sm / GATA2 mut had higher platelet counts (both P = 0.011), while patients with CEBPA dm / TET2 mut had significantly higher hemoglobin levels ( P = 0.009). The CR rate of patients with FLT3 -ITD mutations was significantly lower in the CEBPA sm group than the CEBPA dm group ( P = 0.028). Conclusions CEBPA sm and CEBPA dm 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.