microRNA Deregulation in Myelodysplastic Syndrome.
Robert S Shibata, Jon Nicoll, Ron Paquette, Dinesh Rao. University of California at Los Angeles
Background: Myelodysplastic syndromes (MDS) comprise a heterogeneous of clonal hematopoietic neoplasms that result, paradoxically in a dominant clone in the bone marrow but cytopenias in the peripheral blood. The WHO Classification of Tumours of the Haematopoietic and Lymphoid Tissues (2008, 4th ed) states that MDS “remain among the most challenging of the myeloid neoplasms for proper diagnosis and classification.” Many histologic features have been identified, but the pathogenesis of the syndrome has yet to be fully explored. MicroRNAs, which are recently discovered modulators of gene expression, have been shown to be misexpressed in acute myeloid leukemia and in other bone marrow disorders. Using this cue, we decided to undertake a study to investigate the microRNA expression in myelodysplastic syndromes.
Design: We undertook a preliminary study to investigate the microRNA expression in myelodysplastic syndrome using previously diagnosed specimens from the UCLA medical center department of Hematopathology. 10 MDS bone marrow samples and 4 normal samples (controls) were evaluated using the Agilent Sureprint ®microRNA microarray platform. Following hybridization and data acquisition and normalization, we used Rosetta Resolver ® software to determine statistically significant differences in miRNA expression between control and MDS samples using a T-test-based method.
Results: We found significant upregulation of a set of five microRNAs, and downregulation of another set of three microRNAs. Interestingly, miR-146a, which was recently shown to play a role in the pathogenesis of 5q-syndrome, was amongst the microRNAs that were downregulated in our samples. We are currently in the process of validating our findings by RT-qPCR analysis of bone marrow samples, following which we will correlate the data with clinicopathologic indicators.
Conclusions: These studies promise to reveal an important new facet about the pathogenesis of myelodysplastic syndrome. With additional testing and expanding our initial study, we hope to confirm the miRNA abnormality and provide basis for additional testing that can be utilized to treat this nebulous, yet dangerous entity. Furthermore, we are testing the biological relevance of these microRNAs in hematopoietic cell growth by testing the effects of their overexpression in cell lines.
Monday, February 28, 2011 1:00 PM
Poster Session II # 176, Monday Afternoon