Immunophenotype distinctions of CEBPA mutation subtypes in acute myeloid leukemia
Qiaoxue Liu
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorLing Qi
The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China
Search for more papers by this authorMiao Yang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorXue Zhang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorCorresponding Author
Fei Li
The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Hui Wei
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
National Clinical Research Center for Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jianxiang Wang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
National Clinical Research Center for Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorQiaoxue Liu
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorLing Qi
The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China
Search for more papers by this authorMiao Yang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorXue Zhang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Search for more papers by this authorCorresponding Author
Fei Li
The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Hui Wei
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
National Clinical Research Center for Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorCorresponding Author
Jianxiang Wang
State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
National Clinical Research Center for Blood Disease, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
Correspondence
Fei Li, The Center of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Email: [email protected]
Hui Wei and Jianxiang Wang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Disease, Haihe Laboratory of Cell Ecosystem, Leukemia Center, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing Rd 288, Tianjin 300020, China.
Email: [email protected] and [email protected]
Search for more papers by this authorQiaoxue Liu and Ling Qi contributed equally to this study.
Abstract
Introduction
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.
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 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.
Conclusions
AML with CEBPAdmBZIP, CEBPAdm-woBZIP, and CEBPAsmBZIP shared similar immunophenotypic profiles, whereas profoundly differed from the CEBPAsm-woBZIP and CEBPAwt AML.
CONFLICT OF INTEREST STATEMENT
The authors declare no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
The data sets analyzed during the current study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ijlh14124-sup-0001-FigureS1.tifTIFF image, 7.3 MB | FIGURE S1. Immunophenotypic expression of CEBPAdmBZIP, CEBPAdm-woBZIP, CEBPAsmBZIP, CEBPAsm-woBZIP and CEBPAwt. The immunophenotypic expression profile of CEBPAdmBZIP (n = 198), CEBPAdm-woBZIP (n = 20), CEBPAsmBZIP (n = 54) and CEBPAsm-woBZIP (n = 63) patients in comparison with CEBPAwt samples (n = 632). |
| ijlh14124-sup-0002-FigureS2.tifTIFF image, 6.9 MB | FIGURE S2. The association between immunophenotype and CEBPAdmBZIP in AML. The ranking of immunophenotypic variables by randomforest (A), XGBoost algorithm (B). |
| ijlh14124-sup-0003-FigureS3.tifTIFF image, 6.9 MB | FIGURE S3. The association between immunophenotype and CEBPAsmBZIP in AML. The ranking of immunophenotypic variables by randomforest (A), XGBoost algorithm (B). |
| ijlh14124-sup-0004-FigureS4.tifTIFF image, 6.9 MB | FIGURE S4. The association between immunophenotype and CEBPAdm-woBZIP in AML. The ranking of immunophenotypic variables by randomforest (A), XGBoost algorithm (B). |
| ijlh14124-sup-0005-FigureS5.tifTIFF image, 6.9 MB | FIGURE S5. The association between immunophenotype and CEBPAsm-woBZIP in AML. The ranking of immunophenotypic variables by randomforest (A), XGBoost algorithm (B). |
| ijlh14124-sup-0006-FigureS6.tifTIFF image, 6.9 MB | FIGURE S6. The association between immunophenotype and CEBPAwt in AML. The ranking of immunophenotypic variables by randomforest (A), XGBoost algorithm (B). |
| ijlh14124-sup-0007-FigureS7.tifTIFF image, 6.9 MB | FIGURE S7. The calibration curve of the scoring system in the training data set using 10-fold cross-validation (A) and bootstrap resampling (B). |
| ijlh14124-sup-0008-TableS1.xlsxExcel 2007 spreadsheet , 10.4 KB | TABLE S1. The immunophenotypes of CEBPA mutant and wildtype patients. |
| ijlh14124-sup-0009-TableS2.docxWord 2007 document , 12.4 KB | TABLE S2. Comparison of MPO using multiple imputation methodology. |
| ijlh14124-sup-0010-TableS3.docxWord 2007 document , 12.9 KB | TABLE S3. The scoring system to identify CEBPAdmBZIP in AML based on immunophenotypes. |
| ijlh14124-sup-0011-TableS4.docxWord 2007 document , 12.8 KB | TABLE S4. The sensitivity and specificity when partial immunophenotypes are not detected. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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