Poster Board II-809
Micro-RNAs (miRNAs) are a class of small non-coding single stranded RNAs of 20-22 nucleotides in length. MiRNAs regulate gene expression by binding to the 3' UTR of target mRNAs, which leads to either mRNA degradation or translational inhibition of this target mRNA. MiRNAs play a critical role in cell growth, survival and differentiation and have been suggested to function as tumor suppressor and oncogenes, and/or play a critical role in the pathogenesis of Multiple Myeloma (MM). We investigated miRNA expression in 41 newly diagnosed patients with MM who were included in a clinical trial. MiRNA expression profiling was performed in BM derived CD138 selected plasma cells (PC) obtained from newly diagnosed MM patients with a minimum monoclonal PC purity of > 80%. A quantitative PCR-method (TaqMan low density arrays-microRNA assay', Applied Biosystems) was used for miRNA quantification. The relative expression levels of miRNAs were calculated using the 2-DDCt method and the data was normalized using the endogenous control RNU48. 176/365 miRNAs (48.2%) were expressed in these MM patients. Unsupervised hierarchical clustering based on the average-linkage method and principal component analysis (PCA) was performed in Partek software (Partek Genomics Suite), showing a differential hierarchy for the chromosomal translocation or gain subgroups. When patients with or without chromosome 13 deletions were compared, no correlation was found between expression levels of miRNAs located on chromosome 13 and the deletion status of this chromosome as determined by FISH. Three miRNAs, i.e. miRNA-126, miRNA-145 and miR-517c were identified that were different between MM patients with or without chromosome 13 deletion. These miRNAs were not located on chromosome 13. Likewise, when comparing the miRNA expression in MM patients with or without chromosome 1q gain, the three most differentially expressed miRNAs were miRNA-23a, miRNA-200a# and miRNA-145, which are not on chromosome 1. In addition, miR-18a, located on chromosome 1 was upregulated in MM patients with 1q gain. MM patients with t(4;14) showed differential expression of miRNA-520g, miRNA-28 and miRNA-502. Currently we evaluate potential association of microRNA expression with the clinical response of MM patients to Bortezomib.
In conclusion, our data indicate that miRNAs are differentially expressed in subgroups of MM patients characterized by common cytogenetic abnormalities.
Goldschmidt:Johnson and Johnson: Research Funding, Speakers Bureau. Sonneveld:Johnson and Johnson: Research Funding, Speakers Bureau.
Asterisk with author names denotes non-ASH members.