These authors contributed equally to this work.
Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma
Article first published online: 24 DEC 2008
© 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 13, Issue 7, pages 1248–1260, July 2009
How to Cite
Lawrie, C. H., Chi, J., Taylor, S., Tramonti, D., Ballabio, E., Palazzo, S., Saunders, N. J., Pezzella, F., Boultwood, J., Wainscoat, J. S. and Hatton, C. S. R. (2009), Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma. Journal of Cellular and Molecular Medicine, 13: 1248–1260. doi: 10.1111/j.1582-4934.2008.00628.x
- Issue published online: 30 JUL 2009
- Article first published online: 24 DEC 2008
- Received: October 27, 2008; Accepted: December 3, 2008
- diffuse large B-cell lymphoma;
- follicular lymphoma;
MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n= 80) and follicular lymphoma (FCL) (n= 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17–92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n= 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n= 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n= 7) with FCL cases that had not transformed at a median follow-up of 60 months (n= 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P< 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.