Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) patients with CEBPA double mutation (CEBPAdm ) were associated with distinct immunophenotypes and prognosis. Recently, both International Consensus Classification (ICC) and World Health Organization (WHO) classifications incorporated BZIP single mutations (CEBPAsmBZIP ) into the favorable risk group. However, the immunophenotypes of CEBPAsmBZIP mutations have not been characterized, especially when compared with the immunophenotypes of CEBPAdm . 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 CEBPAdm (198 consisted of mutations in the BZIP region [CEBPAdmBZIP ], 20 were double mutations outside BZIP region [CEBPAdm-woBZIP ]), 117 were CEBPAsm (54 CEBPAsmBZIP and 63 were single mutations outside BZIP region [CEBPAsm-woBZIP ]) and the others were wildtype CEBPA (CEBPAwt ). Patients with CEBPAdmBZIP , CEBPAdm-woBZIP and CEBPAsmBZIP shared the distinct immunophenotype of CD7+ CD34+ MPO+ HLA-DR+ CD19- , in contrast to patients with CEBPAsm-woBZIP and CEBPAwt 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 CEBPAsmBZIP and CEBPAdm and validated it internally and externally. AML with CEBPAdmBZIP , CEBPAdm-woBZIP , and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm-woBZIP and CEBPAwt AML.