Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Abstract Introduction Acute myeloid leukemia (AML) patients with CEBPA double mutation ( CEBPA dm ) were associated with distinct immunophenotypes and prognosis. Recently, both International Consensus Classification (ICC) and World Health Organization (WHO) classifications incorporated BZIP single mutations ( CEBPA smBZIP ) into the favorable risk group. However, the immunophenotypes of CEBPA smBZIP mutations have not been characterized, especially when compared with the immunophenotypes of CEBPA dm . Methods Retrospectively, we investigated and compared the immunophenotypes of AML with CEBPA mutations. Randomforest model and XGBoost algorithm were used to set up a scoring system based on the immunophenotypes of those patients. Results In a total of 967 AML patients: 218 were CEBPA dm (198 consisted of mutations in the BZIP region [ CEBPA dmBZIP ], 20 were double mutations outside BZIP region [ CEBPA dm‐woBZIP ]), 117 were CEBPA sm (54 CEBPA smBZIP and 63 were single mutations outside BZIP region [ CEBPA sm‐woBZIP ]) and the others were wildtype CEBPA ( CEBPA wt ). Patients with CEBPA dmBZIP , CEBPA dm‐woBZIP and CEBPA smBZIP shared the distinct immunophenotype of CD7 + CD34 + MPO + HLA‐DR + CD19 − , in contrast to patients with CEBPA sm‐woBZIP and CEBPA wt who showed reduced expression of CD7, HLA‐DR, MPO, CD34 and a higher expression of CD19. Based on these immunophenotypes, we developed a scoring system to preemptively identify AML with CEBPA smBZIP and CEBPA dm and validated it internally and externally. Conclusions AML with CEBPA dmBZIP , CEBPA dm‐woBZIP , and CEBPA smBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPA sm‐woBZIP and CEBPA wt AML.