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 Charles Greiner, Dennis D. Weisenburger, Patricia Aoun, Sherrie L. Perkins & 3 others Timothy W. McKeithan, Giorgio Inghirami, Wing C. Chan

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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 - Jan 1 2013

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Anaplastic Large-Cell Lymphoma
MicroRNAs
T-cells
Cluster Analysis
anaplastic lymphoma kinase
Down-Regulation
Peripheral T-Cell Lymphoma
T-Lymphocytes
T-Cell Lymphoma

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Liu, C., Iqbal, J., Teruya-Feldstein, J., Shen, Y., Dabrowska, M. J., Dybkaer, K., ... 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

MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma. / Liu, Cuiling; Iqbal, Javeed; Teruya-Feldstein, Julie; Shen, Yulei; Dabrowska, Magdalena Julia; Dybkaer, Karen; Lim, Megan S.; Piva, Roberto; Barreca, Antonella; Pellegrino, Elisa; Spaccarotella, Elisa; Lachel, Cynthia M.; Kucuk, Can; Jiang, Chun Sun; Hu, Xiaozhou; Bhagavathi, Sharathkumar; Greiner, Timothy Charles; Weisenburger, Dennis D.; Aoun, Patricia; Perkins, Sherrie L.; McKeithan, Timothy W.; Inghirami, Giorgio; Chan, Wing C.

In: Blood, Vol. 122, No. 12, 01.01.2013, p. 2083-2092.

Research output: Contribution to journalArticle

Liu, C, Iqbal, J, Teruya-Feldstein, J, Shen, Y, Dabrowska, MJ, Dybkaer, K, Lim, MS, Piva, R, Barreca, A, Pellegrino, E, Spaccarotella, E, Lachel, CM, Kucuk, C, Jiang, CS, Hu, X, Bhagavathi, S, Greiner, TC, Weisenburger, DD, Aoun, P, Perkins, SL, McKeithan, TW, Inghirami, G & Chan, WC 2013, 'MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma', Blood, vol. 122, no. 12, pp. 2083-2092. https://doi.org/10.1182/blood-2012-08-447375
Liu, Cuiling ; Iqbal, Javeed ; Teruya-Feldstein, Julie ; Shen, Yulei ; Dabrowska, Magdalena Julia ; Dybkaer, Karen ; Lim, Megan S. ; Piva, Roberto ; Barreca, Antonella ; Pellegrino, Elisa ; Spaccarotella, Elisa ; Lachel, Cynthia M. ; Kucuk, Can ; Jiang, Chun Sun ; Hu, Xiaozhou ; Bhagavathi, Sharathkumar ; Greiner, Timothy Charles ; Weisenburger, Dennis D. ; Aoun, Patricia ; Perkins, Sherrie L. ; McKeithan, Timothy W. ; Inghirami, Giorgio ; Chan, Wing C. / MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma. In: Blood. 2013 ; Vol. 122, No. 12. pp. 2083-2092.
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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.",
author = "Cuiling Liu and Javeed Iqbal and Julie Teruya-Feldstein and Yulei Shen and Dabrowska, {Magdalena Julia} and Karen Dybkaer and Lim, {Megan S.} and Roberto Piva and Antonella Barreca and Elisa Pellegrino and Elisa Spaccarotella and Lachel, {Cynthia M.} and Can Kucuk and Jiang, {Chun Sun} and Xiaozhou Hu and Sharathkumar Bhagavathi and Greiner, {Timothy Charles} and Weisenburger, {Dennis D.} and Patricia Aoun and Perkins, {Sherrie L.} and McKeithan, {Timothy W.} and Giorgio Inghirami and Chan, {Wing C.}",
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AU - Liu, Cuiling

AU - Iqbal, Javeed

AU - Teruya-Feldstein, Julie

AU - Shen, Yulei

AU - Dabrowska, Magdalena Julia

AU - Dybkaer, Karen

AU - Lim, Megan S.

AU - Piva, Roberto

AU - Barreca, Antonella

AU - Pellegrino, Elisa

AU - Spaccarotella, Elisa

AU - Lachel, Cynthia M.

AU - Kucuk, Can

AU - Jiang, Chun Sun

AU - Hu, Xiaozhou

AU - Bhagavathi, Sharathkumar

AU - Greiner, Timothy Charles

AU - Weisenburger, Dennis D.

AU - Aoun, Patricia

AU - Perkins, Sherrie L.

AU - McKeithan, Timothy W.

AU - Inghirami, Giorgio

AU - Chan, Wing C.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

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