The involvement of microRNA in the pathogenesis of Richter syndrome

Katrien Van Roosbroeck, Recep Bayraktar, Steliana Calin, Johannes Bloehdorn, Mihnea Paul Dragomir, Keishi Okubo, Maria Teresa Sabrina Bertilaccio, Simonetta Zupo, M. James You, Gianluca Gaidano, Davide Rossi, Shih Shih Chen, Nicholas Chiorazzi, Philip A. Thompson, Alessandra Ferrajoli, Francesco Bertoni, Stephan Stilgenbauer, Michael J. Keating, George A. Calin

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Richter syndrome is the name given to the transformation of the most frequent type of leukemia, chronic lymphocytic leukemia, into an aggressive lymphoma. Patients with Richter syndrome have limited response to therapies and dismal survival. The underlying mechanisms of transformation are insufficiently understood and there is a major lack of knowledge regarding the roles of microRNA that have already proven to be causative for most cases of chronic lymphocytic leukemia. Here, by using four types of genomic platforms and independent sets of patients from three institutions, we identified microRNA involved in the transformation of chronic lymphocytic leukemia to Richter syndrome. The expression signature is composed of miR-21, miR-150, miR-146b and miR-181b, with confirmed targets significantly enriched in pathways involved in cancer, immunity and inflammation. In addition, we demonstrated that genomic alterations may account for microRNA deregulation in a subset of cases of Richter syndrome. Furthermore, network analysis showed that Richter transformation leads to a complete rearrangement, resulting in a highly connected microRNA network. Functionally, ectopic overexpression of miR-21 increased proliferation of malignant B cells in multiple assays, while miR-150 and miR-26a were downregulated in a chronic lymphocytic leukemia xenogeneic mouse transplantation model. Together, our results suggest that Richter transformation is associated with significant expression and genomic loci alterations of microRNA involved in both malignancy and immunity.

Original languageEnglish
Pages (from-to)1004-1015
Number of pages12
JournalHaematologica
Volume104
Issue number5
DOIs
Publication statusPublished - May 1 2019

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MicroRNAs
B-Cell Chronic Lymphocytic Leukemia
Immunity
Names
Lymphoma
Neoplasms
Leukemia
B-Lymphocytes
Down-Regulation
Transplantation
Inflammation
Survival
Therapeutics

ASJC Scopus subject areas

  • Hematology

Cite this

Van Roosbroeck, K., Bayraktar, R., Calin, S., Bloehdorn, J., Dragomir, M. P., Okubo, K., ... Calin, G. A. (2019). The involvement of microRNA in the pathogenesis of Richter syndrome. Haematologica, 104(5), 1004-1015. https://doi.org/10.3324/haematol.2018.203828

The involvement of microRNA in the pathogenesis of Richter syndrome. / Van Roosbroeck, Katrien; Bayraktar, Recep; Calin, Steliana; Bloehdorn, Johannes; Dragomir, Mihnea Paul; Okubo, Keishi; Bertilaccio, Maria Teresa Sabrina; Zupo, Simonetta; You, M. James; Gaidano, Gianluca; Rossi, Davide; Chen, Shih Shih; Chiorazzi, Nicholas; Thompson, Philip A.; Ferrajoli, Alessandra; Bertoni, Francesco; Stilgenbauer, Stephan; Keating, Michael J.; Calin, George A.

In: Haematologica, Vol. 104, No. 5, 01.05.2019, p. 1004-1015.

Research output: Contribution to journalArticle

Van Roosbroeck, K, Bayraktar, R, Calin, S, Bloehdorn, J, Dragomir, MP, Okubo, K, Bertilaccio, MTS, Zupo, S, You, MJ, Gaidano, G, Rossi, D, Chen, SS, Chiorazzi, N, Thompson, PA, Ferrajoli, A, Bertoni, F, Stilgenbauer, S, Keating, MJ & Calin, GA 2019, 'The involvement of microRNA in the pathogenesis of Richter syndrome', Haematologica, vol. 104, no. 5, pp. 1004-1015. https://doi.org/10.3324/haematol.2018.203828
Van Roosbroeck K, Bayraktar R, Calin S, Bloehdorn J, Dragomir MP, Okubo K et al. The involvement of microRNA in the pathogenesis of Richter syndrome. Haematologica. 2019 May 1;104(5):1004-1015. https://doi.org/10.3324/haematol.2018.203828
Van Roosbroeck, Katrien ; Bayraktar, Recep ; Calin, Steliana ; Bloehdorn, Johannes ; Dragomir, Mihnea Paul ; Okubo, Keishi ; Bertilaccio, Maria Teresa Sabrina ; Zupo, Simonetta ; You, M. James ; Gaidano, Gianluca ; Rossi, Davide ; Chen, Shih Shih ; Chiorazzi, Nicholas ; Thompson, Philip A. ; Ferrajoli, Alessandra ; Bertoni, Francesco ; Stilgenbauer, Stephan ; Keating, Michael J. ; Calin, George A. / The involvement of microRNA in the pathogenesis of Richter syndrome. In: Haematologica. 2019 ; Vol. 104, No. 5. pp. 1004-1015.
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AU - Dragomir, Mihnea Paul

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