Abstract
Acute myeloid leukemia is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs have important biological functions and play critical roles in pathogenesis and prognosis in a variety of cancers including acute myeloid leukemia. Some reports have constructed risk stratification systems for adult acute myeloid leukemia patients using microRNAs to predict an optimal outcome of patients. However, little has been done in pediatric and adolescent patients. The purpose of this study is to identify a panel of microRNA signature that could predict prognosis in younger cytogenetically normal acute myeloid leukemia patients by analyzing the data from The Cancer Genome Atlas. A total of 59 cytogenetically normal acute myeloid leukemia patients under 21 years with corresponding clinical data were enrolled in our study. Using univariate Cox's model, we found 17 miRNAs were significantly related with overall survival in pediatric and adolescent cytogenetically normal acute myeloid leukemia patients but no clinical parameter was found significant related with overall survival. The multivariate Cox regression identified high expression of hsa-miR-146b was independent poor prognostic factor and high expression of hsa-miR-181c and hsa-miR-4786 appeared to be favorable factors. A model was proposed based on these three miRNAs. Leave-one-out Cross Validation method and Permutation Test was further used to evaluate this model. The function role of has-mir-181c was further studied by carrying out flow cytometry and cell counting kit-8 (CCK-8) in U937 cell line. The results indicate that the 3-microRNA-based signature is a reliable prognostic biomarker for pediatric and adolescent cytogenetically normal acute myeloid leukemia patients.
Highlights
Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous childhood cancer, with an incidence of approximately 7 cases per million children annually [1]
The purpose of this study is to identify a panel of microRNA signature that could predict prognosis in younger cytogenetically normal acute myeloid leukemia patients by analyzing the data from The Cancer Genome Atlas
Using univariate Cox’s model, we found 17 miRNAs were significantly related with overall survival in pediatric and adolescent cytogenetically normal acute myeloid leukemia patients but no clinical parameter was found significant related with overall survival
Summary
Pediatric acute myeloid leukemia (AML) is a rare and heterogeneous childhood cancer, with an incidence of approximately 7 cases per million children annually [1]. Board overlap lies between AML for pediatric patients, adolescents and adults in diagnosis, treatment and prognosis, differences still exist. When harboring NPM1 or CEBPA double mutation, pediatric CN-AML patients are considered favorable prognosis. Emerging evidence suggest miRNAs expression signatures can predict outcomes of various human cancers [3,4,5,6], including hematological malignancies such as adult AML[7] and primary plasma cell leukemia [8]. We conducted a study using the dataset extracted from The Cancer Genome Atlas (TCGA, https:// cancergenome.nih.gov/) and constructed a 3-miRNA signature which may be used to predict the outcome of pediatric and adolescent CN-AML patients
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