TY - JOUR
T1 - MicroRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma
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 C.
AU - Weisenburger, Dennis D.
AU - Aoun, Patricia
AU - Perkins, Sherrie L.
AU - McKeithan, Timothy W.
AU - Inghirami, Giorgio
AU - Chan, Wing C.
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology.
PY - 2013
Y1 - 2013
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.
UR - http://www.scopus.com/inward/record.url?scp=84886286093&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-08-447375
DO - 10.1182/blood-2012-08-447375
M3 - Article
C2 - 23801630
AN - SCOPUS:84886286093
SN - 0006-4971
VL - 122
SP - 2083
EP - 2092
JO - Blood
JF - Blood
IS - 12
ER -