Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

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 .

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.

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.

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.