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

Abstract

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.

Keywords: CEBPA; FLT3; Leukemia; Mutations; Next-generation sequencing.