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

ABSTRACT

Acute myeloid leukemia (AML) with double mutant CEBPA (CEBPAdm) is generally associated with favorable prognosis, but the heterogeneity still blatant and needs further exploration. We aimed to comprehensively analyze the companion genetic abnormalities and their clinical significance in AML patients with CEBPAdm. By performed targeted amplicon sequencing of 58 genes in specimens at the time of initial diagnosis of 609 AML patients, we identified 76 cases (12.5%) were CEBPAdm, and 88.2% of them also carry other gene mutations. There were more additional gene mutations, especially more epigenetic modifiers gene mutations in CEBPAsm than CEBPAdm cases, while GATA2, CSF3R, JAK3, and KIT mutations were exclusively betide in CEBPAdm but not CEBPAsm. Mutations of tyrosine kinase genes confer to adverse prognostic in karyotype normal CEBPAdm AML and provide potential therapeutic targets. The incidence of germline CEBPA mutation in CEBPAdm cases was 5.3% (4/76), including one C-terminal mutation. Deciphering the mutation spectrum of CEBPAdm AML could facilitate an in-depth understanding of the pathogenesis and refine the prognostic classification of this disease entity.