Abstract
BackgroundIdentifying reliable predictive markers is important to make therapeutic decisions, and determine the prognosis for acute myeloid leukemia (AML) patients. However, approximately 50% patients could not be accurately predicted by existing risk factors. It is necessary to identify novel prognostic factors to subdivide the intermediate-risk group or patients without any cytogenetic and molecular abnormalities.MethodsKaplan–Meier and Cox regression were used for survival analyses in three independent AML datasets. Analyses integrating both bioinformatics and ChIP-qPCR experiments were performed to explore the role of CEBPE in regulating the expression of known prognostic factors.ResultsCEBPE expression was an independent predictor for both overall survival (OS) and event-free survival (EFS) of AML patients. Moreover, low-expression of CEBPE was found to be associated with high relapse rate. We also proved that differential expression of CEBPE stratified the wild-type patients of multiple genes into good and poor outcomes. In addition, the results showed that no obvious improvement was achieved by allogeneic transplantation in CEBPE high-expressed group, while the survival rate (both OS and EFS) was significantly increased in transplanted patients that with low expression of CEBPE. Finally, we found that CEBPE might regulate the expression of known prognostic factors by localizing on their promoters.ConclusionOur findings indicated that CEBPE expression was an independent prognostic factor for AML survival, relapse and allogeneic transplantation, which will provide useful information for outcome prediction and therapeutic decisions.
Highlights
Identifying reliable predictive markers is important to make therapeutic decisions, and determine the prognosis for acute myeloid leukemia (AML) patients
We found that CEBPE, as a master transcription regulator of myeloid differentiation, was an independent predictor for both overall survival (OS) and event-free survival (EFS) of AML patients
Low‐expression of CEBPE predicts high relapse rate We evaluated the association between CEBPE expression and relapse rates after complete remission using datasets of The Cancer Genome Atlas (TCGA) and GSE1159, which contained the information of relapse
Summary
Identifying reliable predictive markers is important to make therapeutic decisions, and determine the prognosis for acute myeloid leukemia (AML) patients. It is necessary to identify novel prognostic factors to subdivide the intermediate-risk group or patients without any cytogenetic and molecular abnormalities. Some risk factors were identified by previous studies, and used to predict treatment outcome for AML patients. Some molecular abnormalities, including mutations of TP53, CEBPA, FLT3, DNMT3A were found to provide important prognostic information, especially for CNAML patients [7, 8]. Based on the published data on the prognostic significance of cytogenetic and molecular alterations, ELN stratified the patients into four groups: favorable, intermediate-I, intermediate-II and adverse. This system refined the classification of AML prognosis [6]
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