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 Perkins; Timothy W McKeithan; Giorgio Inghirami; Wing C Chan

doi:10.1182/blood-2012-08-447375

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

Journal article

Open access

Peer reviewed

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, …

Blood, Vol.122(12), pp.2083-2092

09/19/2013

DOI: 10.1182/blood-2012-08-447375

PMCID: PMC3778551

PMID: 23801630

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Abstract

Anaplastic large-cell lymphoma has a unique miRNA signature. The miR-17∼92 is an important downstream effector of ALK oncogenic pathway. 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[+]) ALCLs, 25 ALK-negative (ALK[−]) 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, the miR-17∼92 cluster and its paralogues were also highly expressed in ALK(+) ALCL and may represent important downstream effectors of the ALK oncogenic pathway.

Lymphoid Neoplasia

Details

Title: Subtitle: microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma
Creators: Cuiling Liu - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Javeed Iqbal - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Julie Teruya-Feldstein - Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY
Yulei Shen - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Magdalena Julia Dabrowska - Department of Hematology, Aalborg Hospital, University of Aarhus, Aarhus, Denmark
Karen Dybkaer - Department of Hematology, Aalborg Hospital, University of Aarhus, Aarhus, Denmark
Megan S Lim - Department of Pathology, University of Michigan Health System, Ann Arbor, MI
Roberto Piva - Department of Molecular Biotechnology and Health Sciences, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and
Antonella Barreca - Department of Molecular Biotechnology and Health Sciences, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and
Elisa Pellegrino - Department of Molecular Biotechnology and Health Sciences, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and
Elisa Spaccarotella - Department of Molecular Biotechnology and Health Sciences, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and
Cynthia M Lachel - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Can Kucuk - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Chun-Sun Jiang - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Xiaozhou Hu - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Sharathkumar Bhagavathi - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Timothy C Greiner - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Dennis D Weisenburger - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Patricia Aoun - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Sherrie L Perkins - Department of Pathology, University of Utah, Salt Lake City, UT
Timothy W McKeithan - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Giorgio Inghirami - Department of Molecular Biotechnology and Health Sciences, and Center for Experimental Research and Medical Studies, University of Torino, Torino, Italy; and
Wing C Chan - Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE
Resource Type: Journal article
Publication Details: Blood, Vol.122(12), pp.2083-2092
DOI: 10.1182/blood-2012-08-447375
PMID: 23801630
PMCID: PMC3778551
NLM abbreviation: Blood
ISSN: 0006-4971
eISSN: 1528-0020
Publisher: American Society of Hematology; Washington, DC
Grant note: National Institutes of Health
Language: English
Date published: 09/19/2013
Academic Unit: Pathology
Record Identifier: 9984047635802771

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