Project description:microRNAs, important regulators of cell proliferation and apoptosis, have been shown to be involved in the pathogenesis of acute myeloid leukemia in adulthood AML. However, comprehensive studies in AML of children and adolescents are missing so far. We investigated the miRNA expression profiles of different AML subtypes from 102 pediatric patients in comparison to CD34+ cells from healthy donors and adult AML patients, in order to identify differentially expressed miRNAs. Pediatric samples with core factor binding acute myeloid leukemia and promyelocytic leukemia could be distinguished from each other and MLL rearranged AML subtypes by 9 and 18 miRNAs, respectively. miR-126, -146a, -181a/b, -100, and miR-125b were identified as highest differentially expressed with marked difference of expression between pediatric and adulthood samples of the same cytogenetic subgroup. We next isolated the miRNA targeting complex from t(8;21) and t(15;17) cell line models and comprehensively identified bound miRNAs and targeted mRNAs by a newly devised immunoprecipitation assay followed by rapid microarray detection. Our findings indicate separate binding preferences for the four human Argonaute proteins. Subsequent bioinformatic analysis revealed a concerted action of different Ago proteins in the regulation of AML-relevant pathways, providing an experimental based database of miRNA-mRNA target interaction in Argonaute proteins.
Project description:Purpose: To investigate the transcriptome of primary pediatric acute myeloid leukemia to identify molecular signatures correlated with sensitivity to LV-10 mediated killing Method: RNA sequencing of polyA enriched pediatric acute myeloid leukemia bone marrow aspirates Results: pAML killing sensitivity is associated with the expression of a myeloid maturation signature, while resistant pAMLs expressed a more stem cell-like signature Conclusions: Pediatric acute myeloid leukemia samples have different sensitivities to killing by LV-10 in vitro and the transcriptomes of killing-sensitive and killing-resistant lines differ
Project description:Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics.