MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma

Cuiling Liu, Javeed Iqbal, Julie Teruya-Feldstein, Yulei Shen, Magdalena Julia Dabrowska, Karen Dybkaer, Megan S. Lim, Roberto Piva, Antonella Barreca, Elisa Pellegrino, Elisa Spaccarotella, Cynthia M. Lachel, Can Kucuk, Chun Sun Jiang, Xiaozhou Hu, Sharathkumar Bhagavathi, Timothy C. Greiner, Dennis D. Weisenburger, Patricia Aoun, Sherrie L. PerkinsTimothy W. McKeithan, Giorgio Inghirami, Wing C. Chan

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Anaplastic large-cell lymphomas (ALCLs) encompass at least 2 systemic diseases distinguished by the presence or absence of anaplastic lymphoma kinase (ALK) expression. We performed genome-wide microRNA (miRNA) profiling on 33 ALK-positive (ALK[1]) ALCLs, 25 ALK-negative (ALK[2]) ALCLs, 9 angioimmunoblastic T-cell lymphomas, 11 peripheral T-cell lymphomas not otherwise specified (PTCLNOS), and normal T cells, and demonstrated that ALCLs express many of the miRNAs that are highly expressed in normal T cells with the prominent exception of miR-146a. Unsupervised hierarchical clustering demonstrated distinct clustering of ALCL, PTCL-NOS, and the AITL subtype of PTCL. Cases of ALK(+) ALCL and ALK(-) ALCL were interspersed in unsupervised analysis, suggesting a close relationship at the molecular level. We identified an miRNA signature of 7 miRNAs (5 upregulated: miR- 512-3p, miR-886-5p, miR-886-3p, miR-708, miR-135b; 2 downregulated: miR-146a, miR-155) significantly associated with ALK(+) ALCL cases. In addition, we derived an 11-miRNA signature (4 upregulated: miR-210, miR-197,miR-191, miR-512-3p; 7 downregulated: miR-451, miR-146a, miR-22, miR-455-3p, miR-455-5p, miR-143, miR-494) that differentiates ALK(-) ALCL from other PTCLs. Our in vitro studies identified a set of 32 miRNAs associated with ALK expression. Of these, themiR-17~92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.

Original languageEnglish (US)
Pages (from-to)2083-2092
Number of pages10
JournalBlood
Volume122
Issue number12
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Liu, C., Iqbal, J., Teruya-Feldstein, J., Shen, Y., Dabrowska, M. J., Dybkaer, K., Lim, M. S., Piva, R., Barreca, A., Pellegrino, E., Spaccarotella, E., Lachel, C. M., Kucuk, C., Jiang, C. S., Hu, X., Bhagavathi, S., Greiner, T. C., Weisenburger, D. D., Aoun, P., ... Chan, W. C. (2013). MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma. Blood, 122(12), 2083-2092. https://doi.org/10.1182/blood-2012-08-447375