Genome-Wide Identification of Human Micrornas Located in Leukemia-Associated Genomic Alterations.

Abstract 1287

Poster Board I-309

Cytogenetic alterations, such as amplifications, deletions, or translocations, contribute to myeloid malignancies. MicroRNAs (miRNAs) have emerged as critical regulators of hematopoietic processes and their aberrant expression has been associated with various leukemias. Genomic regions containing sequence alterations and fragile sites in human and mouse cancers are enriched with miRNA genes, however the potentially relevant miRNAs within these regions of genomic instability have not been evaluated on a global basis. Here we investigated miRNAs relevant to acute myeloid leukemia (AML) by: 1) mapping miRNAs within leukemia-associated genomic alterations in models of human AML by high-resolution genome arrays, and 2) evaluated absolute expression of these miRNAs by deep small RNA sequencing. We determined ∼75% (542/706) of miRNAs mapped to leukemia-associated copy-number alterations (CNA) in the cell lines, however, only 20% (99/542) of these miRNAs are expressed at levels above background. Small RNA sequencing allowed us to also identify 28 putative novel miRNAs, 18 of which map to leukemia-associated CNA in the cell lines. Our detailed genomic and small RNA analysis analysis of human leukemic cell lines has identified a subset of leukemia-associated miRNAs warranting further validation.