Repository logo

Oncogenic role of miR-155 in anaplastic large cell lymphoma lacking the t(2;5) translocation.

Change log


Merkel, Olaf 
Hamacher, Frank 
Griessl, Robert 
Grabner, Lisa 
Schiefer, Ana-Iris 


Anaplastic large cell lymphoma (ALCL) is a rare, aggressive, non-Hodgkin's lymphoma that is characterized by CD30 expression and disease onset in young patients. About half of ALCL patients bear the t(2;5)(p23;q35) translocation, which results in the formation of the nucleophosmin-anaplastic lymphoma tyrosine kinase (NPM-ALK) fusion protein (ALCL ALK(+)). However, little is known about the molecular features and tumour drivers in ALK-negative ALCL (ALCL ALK(-)), which is characterized by a worse prognosis. We found that ALCL ALK(-), in contrast to ALCL ALK(+), lymphomas display high miR-155 expression. Consistent with this, we observed an inverse correlation between miR-155 promoter methylation and miR-155 expression in ALCL. However, no direct effect of the ALK kinase on miR-155 levels was observed. Ago2 immunoprecipitation revealed miR-155 as the most abundant miRNA, and enrichment of target mRNAs C/EBPβ and SOCS1. To investigate its function, we over-expressed miR-155 in ALCL ALK(+) cell lines and demonstrated reduced levels of C/EBPβ and SOCS1. In murine engraftment models of ALCL ALK(-), we showed that anti-miR-155 mimics are able to reduce tumour growth. This goes hand-in-hand with increased levels of cleaved caspase-3 and high SOCS1 in these tumours, which leads to suppression of STAT3 signalling. Moreover, miR-155 induces IL-22 expression and suppresses the C/EBPβ target IL-8. These data suggest that miR-155 can act as a tumour driver in ALCL ALK(-) and blocking miR-155 could be therapeutically relevant. Original miRNA array data are to be found in the supplementary material (Table S1).



ALCL, ALK kinase, IL-10, IL-21, IL-22, cytokines, miR-155, Anaplastic Lymphoma Kinase, Animals, Argonaute Proteins, CCAAT-Enhancer-Binding Protein-beta, Case-Control Studies, Caspase 3, Cell Line, Tumor, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 5, DNA Methylation, Gene Expression Regulation, Neoplastic, Genetic Therapy, Humans, Lymphoma, Large-Cell, Anaplastic, Mice, Inbred NOD, Mice, SCID, MicroRNAs, Promoter Regions, Genetic, Receptor Protein-Tyrosine Kinases, STAT3 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling 1 Protein, Suppressor of Cytokine Signaling Proteins, Transfection, Translocation, Genetic, Xenograft Model Antitumor Assays

Journal Title

J Pathol

Conference Name

Journal ISSN


Volume Title



This work was supported by the SCRI-LIMCR GmbH, the “Jubiläumsfond der Österreichischen Nationalbank” (grant-no. 14856 to O.M.), R.G. was supported by grant SFB P021 from the Austrian Science Funds (FWF), L.K. was supported by grant FWF, P26011, R.M. was supported by FWF grants SFB F28 and SFB F47. S.D.T. is a Senior Lecturer supported with funding from Leukemia and Lymphoma Research.