Expression of MicroRNAs in Diffuse Large B Cell Lymphoma is Associated with Immunophenotype, Survival and Transformation from Follicular Lymphoma

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2009 May 6

PMID 19413891

Citations 83

Authors

Charles H Lawrie

Jianxiang Chi

Stephen Taylor

Daniela Tramonti

Erica Ballabio

Stefano Palazzo

Nigel J Saunders

Francesco Pezzella

Jacqueline Boultwood

James S Wainscoat

Christian S R Hatton

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Deregulation mechanisms and therapeutic opportunities of p53-responsive microRNAs in diffuse large B-cell lymphoma.

Voropaeva E, Orlov Y, Loginova A, Seregina O, Maksimov V, Pospelova T PeerJ. 2025; 13():e18661.

PMID: 39802185 PMC: 11720970. DOI: 10.7717/peerj.18661.

The Role of microRNA-155 as a Biomarker in Diffuse Large B-Cell Lymphoma.

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PMID: 39767565 PMC: 11673977. DOI: 10.3390/biomedicines12122658.

Molecular Biomarkers in Prediction of High-Grade Transformation and Outcome in Patients with Follicular Lymphoma: A Comprehensive Systemic Review.

Enemark M, Hemmingsen J, Jensen M, Kridel R, Ludvigsen M Int J Mol Sci. 2024; 25(20).

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Let7i A key player and a promising biomarker in diseases.

Hou J, Sun X Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023; 48(6):909-919.

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References

Xiao C, Calado D, Galler G, Thai T, Patterson H, Wang J . MiR-150 controls B cell differentiation by targeting the transcription factor c-Myb. Cell. 2007; 131(1):146-59. DOI: 10.1016/j.cell.2007.07.021. View

Colomo L, Lopez-Guillermo A, Perales M, Rives S, Martinez A, Bosch F . Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood. 2002; 101(1):78-84. DOI: 10.1182/blood-2002-04-1286. View

Calin G, Sevignani C, Dumitru C, Hyslop T, Noch E, Yendamuri S . Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004; 101(9):2999-3004. PMC: 365734. DOI: 10.1073/pnas.0307323101. View

Michael M, O Connor S, van Holst Pellekaan N, Young G, James R . Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 2003; 1(12):882-91. View

Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S . BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol. 2005; 207(2):243-9. DOI: 10.1002/path.1825. View

Aref S, Mabed M, Zalata K, Sakrana M, El Askalany H . The interplay between c-Myc oncogene expression and circulating vascular endothelial growth factor (sVEGF), its antagonist receptor, soluble Flt-1 in diffuse large B cell lymphoma (DLBCL): relationship to patient outcome. Leuk Lymphoma. 2004; 45(3):499-506. DOI: 10.1080/10428190310001607151. View

Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk R, Cuppen E . Phylogenetic shadowing and computational identification of human microRNA genes. Cell. 2005; 120(1):21-4. DOI: 10.1016/j.cell.2004.12.031. View

le Sage C, Nagel R, Egan D, Schrier M, Mesman E, Mangiola A . Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation. EMBO J. 2007; 26(15):3699-708. PMC: 1949005. DOI: 10.1038/sj.emboj.7601790. View

Zhou B, Wang S, Mayr C, Bartel D, Lodish H . miR-150, a microRNA expressed in mature B and T cells, blocks early B cell development when expressed prematurely. Proc Natl Acad Sci U S A. 2007; 104(17):7080-5. PMC: 1855395. DOI: 10.1073/pnas.0702409104. View

10.

Lawrie C . MicroRNAs and haematology: small molecules, big function. Br J Haematol. 2007; 137(6):503-12. DOI: 10.1111/j.1365-2141.2007.06611.x. View

11.

Eis P, Tam W, Sun L, Chadburn A, Li Z, Gomez M . Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005; 102(10):3627-32. PMC: 552785. DOI: 10.1073/pnas.0500613102. View

12.

Iorio M, Ferracin M, Liu C, Veronese A, Spizzo R, Sabbioni S . MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005; 65(16):7065-70. DOI: 10.1158/0008-5472.CAN-05-1783. View

13.

Alizadeh A, Eisen M, Davis R, Ma C, Lossos I, Rosenwald A . Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000; 403(6769):503-11. DOI: 10.1038/35000501. View

14.

Nie K, Gomez M, Landgraf P, Garcia J, Liu Y, Tan L . MicroRNA-mediated down-regulation of PRDM1/Blimp-1 in Hodgkin/Reed-Sternberg cells: a potential pathogenetic lesion in Hodgkin lymphomas. Am J Pathol. 2008; 173(1):242-52. PMC: 2438301. DOI: 10.2353/ajpath.2008.080009. View

15.

Montoto S, Davies A, Matthews J, Calaminici M, Norton A, Amess J . Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007; 25(17):2426-33. DOI: 10.1200/JCO.2006.09.3260. View

16.

He L, Thomson J, Hemann M, Hernando-Monge E, Mu D, Goodson S . A microRNA polycistron as a potential human oncogene. Nature. 2005; 435(7043):828-33. PMC: 4599349. DOI: 10.1038/nature03552. View

17.

Lawrie C . MicroRNA expression in lymphoma. Expert Opin Biol Ther. 2007; 7(9):1363-74. DOI: 10.1517/14712598.7.9.1363. View

18.

Kim V . MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005; 6(5):376-85. DOI: 10.1038/nrm1644. View

19.

Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O . Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet. 2005; 37(7):766-70. DOI: 10.1038/ng1590. View

20.

Davis R, Brown K, Siebenlist U, Staudt L . Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med. 2001; 194(12):1861-74. PMC: 2193582. DOI: 10.1084/jem.194.12.1861. View