The MicroRNA Expression Signature of Lymphoplasmacytic Lymphoma Is Distinct from Chronic Lymphocytic Leukemia
I Gurevich, M Johnson, C Eiken, S Vadhan-Raj, M Fernandez, M Nguyen, H Kantarjian, LJ Medeiros, CE Bueso-Ramos. The University of Texas MD Anderson Cancer Center, Houston, TX
Background: MicroRNAs are a newly discovered class of short (19-25 nt), naturally occurring, single-stranded RNA molecules that regulate the expression of target genes post-transcriptionally, mostly by repressing translation or inducing mRNA degradation. MicroRNAs can function as both oncogenes or tumor suppressor genes, or as both at the same time, playing an important role in the development of solid and hematopoetic malignancies. To date, the microRNA expression signature of lymphoplasmacytic lymphoma (LPL) has not been assessed. The goal of this study was to identify the microRNA expression signature of LPL and compare this signature to that of chronic lymphocytic leukemia (CLL). Unique patterns of altered microRNA expression may allow a better understanding of the molecular pathogenesis of LPL, and also may be useful in differential diagnoses, assessment of prognosis, and prediction of therapeutic response.
Design: 10 lymphoma samples, 5 LPL and 5 CLL, were the study group. All patients were adults, had diffuse bone marrow involvement, and were treated at M. D. Anderson Cancer Center. The patients with LPL all had a serum IgM paraprotein and also fit the criteria for Waldesntrom macroglobulinemia. Flow cytometric immunophenotypic analysis of both the LPL and CLL cases showed a mature B-cell immunophenotype; the CLL cases were CD5+ and CD23+. The recoverAll TM Total Nucleic Acid Isolation Kit (Ambion, Inc) was used for microRNA isolation from formalin-fixed, paraffin-embedded bone marrow biopsy specimens. New high performance microfluidic custom microarray platforms were used to generate microRNA signatures. MicroRNA quality was assessed by TaqMan reverse transcriptase real time PCR for ubiquitous microRNAs.
Results: MiR-155 and miR-423-5p were significantly down-regulated in LPL compared with CLL (p-value< 0.01), and miR-638 was strongly up-regulated in LPL compared with CLL with an 8-fold statistically significant difference (p-value<0.01). The miR-155 and miR-638 results were confirmed by RT- PCR.
Conclusions: Our results indicate that specific microRNA signatures exist for LPL and CLL that can be helpful in discriminating LPL from CLL in difficult cases. In particular, miR-155, miR-423-5p, and miR-638 are differentially expressed in LPL and CLL.
Monday, March 9, 2009 8:30 AM
Platform Session: Section D, Monday Morning