Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia

Author:

Liu Qiaoxue1ORCID,Qi Ling2,Yang Miao1,Zhang Xue1,Li Fei2,Wei Hui1345,Wang Jianxiang1345

Affiliation:

1. State Key Laboratory of Experimental Hematology Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China

2. The Center of Hematology The First Affiliated Hospital of Nanchang University Nanchang China

3. National Clinical Research Center for Blood Disease Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China

4. Haihe Laboratory of Cell Ecosystem Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China

5. Leukemia Center, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin China

Abstract

AbstractIntroductionAcute 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.MethodsRetrospectively, 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.ResultsIn 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.ConclusionsAML with CEBPAdmBZIP, CEBPAdm‐woBZIP, and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm‐woBZIP and CEBPAwt AML.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

Biochemistry (medical),Clinical Biochemistry,Hematology,General Medicine

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