Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

Javeed Iqbal, George Wright, Chao Wang, Andreas Rosenwald, Randy D. Gascoyne, Dennis D. Weisenburger, Timothy C. Greiner, Lynette Smith, Shuangping Guo, Ryan A. Wilcox, Bin Tean Teh, Soon Thye Lim, Soon Yong Tan, Lisa Rimsza, Elaine S. Jaffe, Elias Campo, Antonio Martinez, Jan Delabie, Rita M. Braziel, James R. CookRaymond R. Tubbs, German Ott, Eva Geissinger, Philippe Gaulard, Pier Paolo Piccaluga, Stefano A. Pileri, Wing Y. Au, Shigeo Nakamura, Masao Seto, Francoise Berger, Laurence De Leval, Joseph M. Connors, James Armitage, Julie Vose, Wing C. Chan, Louis M. Staudt

Research output: Contribution to journalArticle

171 Citations (Scopus)

Abstract

Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature-within the TBX21 subgroup also showed poor clinical outcome ( P = .05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

Original languageEnglish (US)
Pages (from-to)2915-2923
Number of pages9
JournalBlood
Volume123
Issue number19
DOIs
StatePublished - May 8 2014
Externally publishedYes

Fingerprint

Peripheral T-Cell Lymphoma
T-cells
Transcriptome
Gene expression
Extranodal NK-T-Cell Lymphoma
Anaplastic Large-Cell Lymphoma
Cellular Microenvironment
Adult T Cell Leukemia Lymphoma
Tumors
Tumor Microenvironment
T-Cell Lymphoma
Natural Killer Cells
Lymphoma
Neoplasms
Immunohistochemistry
Mutation
Classifiers
Genes
Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology
  • Medicine(all)

Cite this

Iqbal, J., Wright, G., Wang, C., Rosenwald, A., Gascoyne, R. D., Weisenburger, D. D., ... Staudt, L. M. (2014). Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood, 123(19), 2915-2923. https://doi.org/10.1182/blood-2013-11-536359

Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. / Iqbal, Javeed; Wright, George; Wang, Chao; Rosenwald, Andreas; Gascoyne, Randy D.; Weisenburger, Dennis D.; Greiner, Timothy C.; Smith, Lynette; Guo, Shuangping; Wilcox, Ryan A.; Teh, Bin Tean; Lim, Soon Thye; Tan, Soon Yong; Rimsza, Lisa; Jaffe, Elaine S.; Campo, Elias; Martinez, Antonio; Delabie, Jan; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Ott, German; Geissinger, Eva; Gaulard, Philippe; Piccaluga, Pier Paolo; Pileri, Stefano A.; Au, Wing Y.; Nakamura, Shigeo; Seto, Masao; Berger, Francoise; De Leval, Laurence; Connors, Joseph M.; Armitage, James; Vose, Julie; Chan, Wing C.; Staudt, Louis M.

In: Blood, Vol. 123, No. 19, 08.05.2014, p. 2915-2923.

Research output: Contribution to journalArticle

Iqbal, J, Wright, G, Wang, C, Rosenwald, A, Gascoyne, RD, Weisenburger, DD, Greiner, TC, Smith, L, Guo, S, Wilcox, RA, Teh, BT, Lim, ST, Tan, SY, Rimsza, L, Jaffe, ES, Campo, E, Martinez, A, Delabie, J, Braziel, RM, Cook, JR, Tubbs, RR, Ott, G, Geissinger, E, Gaulard, P, Piccaluga, PP, Pileri, SA, Au, WY, Nakamura, S, Seto, M, Berger, F, De Leval, L, Connors, JM, Armitage, J, Vose, J, Chan, WC & Staudt, LM 2014, 'Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma', Blood, vol. 123, no. 19, pp. 2915-2923. https://doi.org/10.1182/blood-2013-11-536359
Iqbal J, Wright G, Wang C, Rosenwald A, Gascoyne RD, Weisenburger DD et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood. 2014 May 8;123(19):2915-2923. https://doi.org/10.1182/blood-2013-11-536359
Iqbal, Javeed ; Wright, George ; Wang, Chao ; Rosenwald, Andreas ; Gascoyne, Randy D. ; Weisenburger, Dennis D. ; Greiner, Timothy C. ; Smith, Lynette ; Guo, Shuangping ; Wilcox, Ryan A. ; Teh, Bin Tean ; Lim, Soon Thye ; Tan, Soon Yong ; Rimsza, Lisa ; Jaffe, Elaine S. ; Campo, Elias ; Martinez, Antonio ; Delabie, Jan ; Braziel, Rita M. ; Cook, James R. ; Tubbs, Raymond R. ; Ott, German ; Geissinger, Eva ; Gaulard, Philippe ; Piccaluga, Pier Paolo ; Pileri, Stefano A. ; Au, Wing Y. ; Nakamura, Shigeo ; Seto, Masao ; Berger, Francoise ; De Leval, Laurence ; Connors, Joseph M. ; Armitage, James ; Vose, Julie ; Chan, Wing C. ; Staudt, Louis M. / Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. In: Blood. 2014 ; Vol. 123, No. 19. pp. 2915-2923.
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abstract = "Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50{\%} of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33{\%}; 40/121) or TBX21 (49{\%}; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature-within the TBX21 subgroup also showed poor clinical outcome ( P = .05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).",
author = "Javeed Iqbal and George Wright and Chao Wang and Andreas Rosenwald and Gascoyne, {Randy D.} and Weisenburger, {Dennis D.} and Greiner, {Timothy C.} and Lynette Smith and Shuangping Guo and Wilcox, {Ryan A.} and Teh, {Bin Tean} and Lim, {Soon Thye} and Tan, {Soon Yong} and Lisa Rimsza and Jaffe, {Elaine S.} and Elias Campo and Antonio Martinez and Jan Delabie and Braziel, {Rita M.} and Cook, {James R.} and Tubbs, {Raymond R.} and German Ott and Eva Geissinger and Philippe Gaulard and Piccaluga, {Pier Paolo} and Pileri, {Stefano A.} and Au, {Wing Y.} and Shigeo Nakamura and Masao Seto and Francoise Berger and {De Leval}, Laurence and Connors, {Joseph M.} and James Armitage and Julie Vose and Chan, {Wing C.} and Staudt, {Louis M.}",
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T1 - Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma

AU - Iqbal, Javeed

AU - Wright, George

AU - Wang, Chao

AU - Rosenwald, Andreas

AU - Gascoyne, Randy D.

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy C.

AU - Smith, Lynette

AU - Guo, Shuangping

AU - Wilcox, Ryan A.

AU - Teh, Bin Tean

AU - Lim, Soon Thye

AU - Tan, Soon Yong

AU - Rimsza, Lisa

AU - Jaffe, Elaine S.

AU - Campo, Elias

AU - Martinez, Antonio

AU - Delabie, Jan

AU - Braziel, Rita M.

AU - Cook, James R.

AU - Tubbs, Raymond R.

AU - Ott, German

AU - Geissinger, Eva

AU - Gaulard, Philippe

AU - Piccaluga, Pier Paolo

AU - Pileri, Stefano A.

AU - Au, Wing Y.

AU - Nakamura, Shigeo

AU - Seto, Masao

AU - Berger, Francoise

AU - De Leval, Laurence

AU - Connors, Joseph M.

AU - Armitage, James

AU - Vose, Julie

AU - Chan, Wing C.

AU - Staudt, Louis M.

PY - 2014/5/8

Y1 - 2014/5/8

N2 - Peripheral T-cell lymphoma (PTCL) encompasses a heterogeneous group of neoplasms with generally poor clinical outcome. Currently 50% of PTCL cases are not classifiable: PTCL-not otherwise specified (NOS). Gene-expression profiles on 372 PTCL cases were analyzed and robust molecular classifiers and oncogenic pathways that reflect the pathobiology of tumor cells and their microenvironment were identified for major PTCL-entities, including 114 angioimmunoblastic T-cell lymphoma (AITL), 31 anaplastic lymphoma kinase (ALK)-positive and 48 ALK-negative anaplastic large cell lymphoma, 14 adult T-cell leukemia/lymphoma and 44 extranodal NK/T-cell lymphoma that were further separated into NK-cell and gdT-cell lymphomas. Thirty-seven percent of morphologically diagnosed PTCL-NOS cases were reclassified into other specific subtypes by molecular signatures. Reexamination, immunohistochemistry, and IDH2 mutation analysis in reclassified cases supported the validity of the reclassification. Two major molecular subgroups can be identified in the remaining PTCL-NOS cases characterized by high expression of either GATA3 (33%; 40/121) or TBX21 (49%; 59/121). The GATA3 subgroup was significantly associated with poor overall survival (P = .01). High expression of cytotoxic gene-signature-within the TBX21 subgroup also showed poor clinical outcome ( P = .05). InAITL, high expression of several signatures associated with the tumor microenvironment was significantly associated with outcome. A combined prognostic score was predictive of survival in an independent cohort (P = .004).

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