Abstract
Acute myeloid leukemia (AML) in children is a complex and heterogeneous disease. The identification of reliable and stable molecular biomarkers for diagnosis, especially early diagnosis, remains a significant therapeutic challenge. Aberrant microRNA expression could be used for cancer diagnosis and treatment selection. Here, we describe a novel bioinformatics model for the prediction of microRNA biomarkers for the diagnosis of paediatric AML based on computational functional analysis of the microRNA regulatory network substructure. microRNA-196b, microRNA-155 and microRNA-25 were identified as putative diagnostic biomarkers for pediatric AML. Further systematic analysis confirmed the association of the predicted microRNAs with the leukemogenesis of AML. In vitro q-PCR experiments showed that microRNA-155 is significantly overexpressed in children with AML and microRNA-196b is significantly overexpressed in subgroups M4-M5 of the French-American-British classification system. These results suggest that microRNA-155 is a potential diagnostic biomarker for all subgroups of paediatric AML, whereas microRNA-196b is specific for subgroups M4-M5.
Highlights
Acute myeloid leukemia (AML) is a rare and heterogeneous cancer that arises from the clonal transformation of hematopoietic precursors
To confirm the novel out degree (NOD) and transcription factor percentage (TFP) value distribution features of miRNAs, we investigated these two values for miRNAs in the context of the miRNA-mRNA network from the POMA model
TFP distribution is shown in Figure 2B, which indicates that the majority of miRNAs with larger TFP values were potential biomarkers
Summary
Acute myeloid leukemia (AML) is a rare and heterogeneous cancer that arises from the clonal transformation of hematopoietic precursors. It is the most common type of leukaemia diagnosed during infancy, accounting for 15–20% of cases of acute childhood leukemia. Approximately one third of patients experience relapses with modern intensive chemotherapy protocols [2, 3]. The improvements in AML can be largely attributed to intensive use of conventional cytotoxic chemotherapy, whose late effects cause significant morbidity for many survivors. In contrast to the high OS rate (> 80%) of acute lymphocytic leukemia (ALL), the improvements in AML diagnosis and therapy have been limited. Novel approaches to the diagnosis and treatment of AML are needed [4]
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