Classification of pediatric acute myeloid leukemia based on miRNA expression profiles

ABSTRACT: Pediatric acute myeloid leukemia (AML) is a heterogeneous disease with respect to biology as well as outcome. In this study, we investigated whether known biological subgroups of pediatric AML are reflected by a common microRNA (miRNA) expression pattern. We assayed 665 miRNAs in 165 pediatric AML samples. First, unsupervised clustering was performed to identify patient clusters with common miRNA expression profiles. Our analysis unraveled 14 clusters, seven of which had a known (cyto-)genetic denominator. Finally, a robust classifier was constructed to discriminate six known molecular aberration groups: 11q23-rearrangements, t(8;21)(q22;q22), inv(16)(p13q22), t(15;17)(q21;q22), NPM1 and CEBPA mutations. The classifier achieved accuracies of 89%, 95%, 95%, 98%, 91% and 96%, respectively. Although lower sensitivities were obtained for the NPM1 and CEBPA (32% and 66%), relatively high sensitivities (84%-94%) were attained for the rest. Specificity was high in all groups (87%-100%). Due to a robust double-loop cross validation procedure we employed, the classifier only used expression of 47 miRNAs to generate the aforementioned accuracies. To validate the 47 miRNA signatures, we applied them to a publicly available adult AML dataset. Despite partial overlap of miRNA platforms and known molecular differences between pediatric and adult AML, the signatures performed reasonably well. This corroborates our claim that the reported miRNA signatures are not dominated by sample size bias in the pediatric AML dataset. We conclude that cytogenetic subtypes of pediatric AML have distinct miRNA expression patterns. Note that, reproducibility of the miRNA signatures in adult dataset suggests that the respective aberrations have a similar biology both in pediatric and adult AML

ORGANISM(S): Homo sapiens

PROVIDER: GSE94066 | GEO | 2017/04/01

SECONDARY ACCESSION(S): PRJNA368712

REPOSITORIES: GEO