Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis

Javeed Iqbal, Yulei Shen, Yanyan Liu, Kai Fu, Elaine S. Jaffe, Cuiling Liu, Zhongfeng Liu, Cynthia M. Lachel, Karen Deffenbacher, Timothy Charles Greiner, Julie Marie Vose, Sharathkumar Bhagavathi, Louis M. Staudt, Lisa Rimsza, Andreas Rosenwald, German Ott, Jan Delabie, Elias Campo, Rita M. Braziel, James R. CookRaymond R. Tubbs, Randy D. Gascoyne, James Olen Armitage, Dennis D. Weisenburger, Timothy W. McKeithan, Wing C. Chan

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/ lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.

Original languageEnglish (US)
Pages (from-to)4939-4948
Number of pages10
JournalBlood
Volume119
Issue number21
DOIs
StatePublished - May 24 2012

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Mantle-Cell Lymphoma
MicroRNAs
Genes
Genome
Cyclin D1
Lymphoid Leukemia
Cells
B-Cell Chronic Lymphocytic Leukemia
Lymphoma
Classifiers
B-Lymphocyte Subsets
Deregulation
B-Cell Lymphoma
Stromal Cells
Paraffin
Cluster Analysis
Real-Time Polymerase Chain Reaction
B-Lymphocytes
Throughput

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis. / Iqbal, Javeed; Shen, Yulei; Liu, Yanyan; Fu, Kai; Jaffe, Elaine S.; Liu, Cuiling; Liu, Zhongfeng; Lachel, Cynthia M.; Deffenbacher, Karen; Greiner, Timothy Charles; Vose, Julie Marie; Bhagavathi, Sharathkumar; Staudt, Louis M.; Rimsza, Lisa; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Gascoyne, Randy D.; Armitage, James Olen; Weisenburger, Dennis D.; McKeithan, Timothy W.; Chan, Wing C.

In: Blood, Vol. 119, No. 21, 24.05.2012, p. 4939-4948.

Research output: Contribution to journalArticle

Iqbal, J, Shen, Y, Liu, Y, Fu, K, Jaffe, ES, Liu, C, Liu, Z, Lachel, CM, Deffenbacher, K, Greiner, TC, Vose, JM, Bhagavathi, S, Staudt, LM, Rimsza, L, Rosenwald, A, Ott, G, Delabie, J, Campo, E, Braziel, RM, Cook, JR, Tubbs, RR, Gascoyne, RD, Armitage, JO, Weisenburger, DD, McKeithan, TW & Chan, WC 2012, 'Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis', Blood, vol. 119, no. 21, pp. 4939-4948. https://doi.org/10.1182/blood-2011-07-370122
Iqbal, Javeed ; Shen, Yulei ; Liu, Yanyan ; Fu, Kai ; Jaffe, Elaine S. ; Liu, Cuiling ; Liu, Zhongfeng ; Lachel, Cynthia M. ; Deffenbacher, Karen ; Greiner, Timothy Charles ; Vose, Julie Marie ; Bhagavathi, Sharathkumar ; Staudt, Louis M. ; Rimsza, Lisa ; Rosenwald, Andreas ; Ott, German ; Delabie, Jan ; Campo, Elias ; Braziel, Rita M. ; Cook, James R. ; Tubbs, Raymond R. ; Gascoyne, Randy D. ; Armitage, James Olen ; Weisenburger, Dennis D. ; McKeithan, Timothy W. ; Chan, Wing C. / Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis. In: Blood. 2012 ; Vol. 119, No. 21. pp. 4939-4948.
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title = "Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis",
abstract = "miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/ lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.",
author = "Javeed Iqbal and Yulei Shen and Yanyan Liu and Kai Fu and Jaffe, {Elaine S.} and Cuiling Liu and Zhongfeng Liu and Lachel, {Cynthia M.} and Karen Deffenbacher and Greiner, {Timothy Charles} and Vose, {Julie Marie} and Sharathkumar Bhagavathi and Staudt, {Louis M.} and Lisa Rimsza and Andreas Rosenwald and German Ott and Jan Delabie and Elias Campo and Braziel, {Rita M.} and Cook, {James R.} and Tubbs, {Raymond R.} and Gascoyne, {Randy D.} and Armitage, {James Olen} and Weisenburger, {Dennis D.} and McKeithan, {Timothy W.} and Chan, {Wing C.}",
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T1 - Genome-wide miRNA profiling of mantle cell lymphoma reveals a distinct subgroup with poor prognosis

AU - Iqbal, Javeed

AU - Shen, Yulei

AU - Liu, Yanyan

AU - Fu, Kai

AU - Jaffe, Elaine S.

AU - Liu, Cuiling

AU - Liu, Zhongfeng

AU - Lachel, Cynthia M.

AU - Deffenbacher, Karen

AU - Greiner, Timothy Charles

AU - Vose, Julie Marie

AU - Bhagavathi, Sharathkumar

AU - Staudt, Louis M.

AU - Rimsza, Lisa

AU - Rosenwald, Andreas

AU - Ott, German

AU - Delabie, Jan

AU - Campo, Elias

AU - Braziel, Rita M.

AU - Cook, James R.

AU - Tubbs, Raymond R.

AU - Gascoyne, Randy D.

AU - Armitage, James Olen

AU - Weisenburger, Dennis D.

AU - McKeithan, Timothy W.

AU - Chan, Wing C.

PY - 2012/5/24

Y1 - 2012/5/24

N2 - miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/ lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.

AB - miRNA deregulation has been implicated in the pathogenesis of mantle cell lymphoma (MCL). Using a high-throughput quantitative real-time PCR platform, we performed miRNA profiling on cyclin D1-positive MCL (n = 30) and cyclin D1-negative MCL (n = 7) and compared them with small lymphocytic leukemia/ lymphoma (n = 12), aggressive B-cell lymphomas (n = 138), normal B-cell subsets, and stromal cells. We identified a 19-miRNA classifier that included 6 up-regulated miRNAs and 13 down regulated miRNA that was able to distinguish MCL from other aggressive lymphomas. Some of the up-regulated miRNAs are highly expressed in naive B cells. This miRNAclassifier showed consistent results in formalinfixed paraffin-embedded tissues and was able to distinguish cyclin D1-negative MCL from other lymphomas. A 26-miRNA classifier could distinguish MCL from small lymphocytic leukemia/lymphoma, dominated by 23 up-regulated miRNAs in MCL. Unsupervised hierarchical clustering of MCL patients demonstrated a cluster characterized by high expression of miRNAs from the polycistronic miR17-92 cluster and its paralogs, miR-106a-363 and miR-106b-25, and associated with high proliferation gene signature. The other clusters showed enrichment of stroma-associated miRNAs, and also had higher expression of stroma-associated genes. Our clinical outcome analysis in the present study suggested that miRNAs can serve as prognosticators.

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