Multiple Myeloma Patients with 13q14 Deletion Show a Significant Downregulation of MicroRNA Gene Mir16a but Not of Mir15a
A Malik, SU Bozkurt, AA Toor, S Alkan. Loyola Univ Med Ctr, Maywood, IL
Background: Multiple myeloma (MM) is an incurable malignancy characterized by a proliferation of clonal plasma cells. The plasma cells often harbor karyotypic abnormalities such as deletion of chromosome 13q14 (13q14-del), commonly detected by cytogenetics and FISH studies in of patients with MM. Despite well known association of 13q14-del with poor prognosis in MM, the exact role of genes associated with this locus in MM is unknown. MicroRNAs (miRNAs) are naturally occurring, highly conserved families of transcripts (1825 nt in length) that are processed from larger hairpin precursors and play an important role in cellular growth in normal and neoplastic cells. Recent evidence indicates that miRNAs can also function both as a tumor suppressor and oncogene.
Design: A total of 23 newly diagnosed MM patients with standard karyotyping and FISH assays with viable frozen material for miRNA analysis was available. 7 patients had 13q14-del with standard karyotyping.All 7 and additional 1 more patients showed 13q14 del by FISH using a probe D13S319 were selected for miRNA analysis. Following positive selection of plasma cells by CD138 purification, miRNA were isolated and subjected to Taqman reverse transcpitase real time PCR (RT-PCR). Changes in miRNA mir16a and mir15a expression in paired sample were assessed in triplicate ABI 7500 instrument.
Results: The real- time PCR analysis of miRNA showed that the average number of miR16a copies was 428 copies per cell in 13q14-del MM samples (range 14 to 1176 copies per cell), while it averaged 7790 copies per cell in 13q14 non-deleted patients (831 to 30573 copies per cell , P=0.0003). In contrast to the miR16a, the miR15a levels in general were very low in all myeloma cases. The miR15a averaged 11 copies per cell in the 13q14-del samples while it averaged 45 copies.
Conclusions: miR16a was downregulated in of the majority of MM samples with the 13q14 deletion as compared to those MM cells that did not harbour this deletion. Therefore, miR16a may have a critical role in the pathogenetic effect of 13q14 deletion in MM particularly considering a recent evidence demonstrating miR16 G0/G1 arrest and decreased cell growth.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 207, Wednesday Morning