High-throughput functional characterization of miRNAs in cytogenetically defined AML subgroups

Acute Myeloid Leukemia (AML) is a common type of cancer in children and adolescents, characterized by recurrent cytogenetic abnormalities. MicroRNAs (miRNAs) have shown to play a major role in leukemogenesis.

We conducted a functional anti-miR screening to complement a previous global gene expression profiling in cytogenetically characterized AML subgroups (MLL-rearranged, t(8;21), t(15;17)). Four leukemia cell lines with the corresponding karyotypes were transfected with 470 anti-miRs and cell viability was assessed after 72h and 96h. Bioinformatic analysis (B score calculation) revealed a total of 187 candidates. 4 anti-miRs lead to a significant growth disadvantage in THP1 and ML2 (MLL-rearranged), 41 in NB4 (t(15;17)) and 38 in KASUMI1 (t(8;21)). Of those 1, 3, and 4 miRNAs were indeed overexpressed in MLL-rearranged, t(15;17) and t(8;21) patient samples, respectively, in a cohort of 165 pediatric AMLs. Thus, by combining forward genetics and global gene expression profiling we identified novel oncomiR candidates, which are currently assessed for their leukemogenic potential in vitro and in vivo.