Somatic Bzip Mutations Of Cebpa Are Associated With Favorable Outcome Regardless Of Presence As Single Vs. Double Mutation

Somatic mutations of CEBPA in AML are present at similar rates in all age groups and have been shown to be associated with favorable outcome. The most common cooperating variant in CEBPA mutations is a second CEBPA mutation, where the cooperation of TAD and bZip mutations lead to a highly penetrant variant which is sufficient for malignant transformation. Data suggested that only double CEBPA mutations (CEBPA-dm) were associated with favorable outcome. Currently, WHO classification of AML includes CEBPA-dm as a diagnostic entity in AML. We previously reported that in children and young adults, somatic single CEBPA mutations, which almost exclusively occurred in the bZip domain, had similar outcomes to CEBPA-dm patients. We have also shown that CSF3R and GATA2 mutations occur in childhood AML and are highly associated with CEBPA mutations. In this large analysis, we sought to define the prognostic impact of CEBPA-dm vs single bZip mutations and evaluate the impact of common co-occurring mutations.