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

被引：403

作者：

Iqbal, Javeed ^{[1
]}

Wright, George ^{[2
]}

Wang, Chao ^{[1
]}

Rosenwald, Andreas ^{[3
]}

Gascoyne, Randy D. ^{[4
]}

Weisenburger, Dennis D. ^{[5
]}

Greiner, Timothy C. ^{[1
]}

Smith, Lynette ^{[6
]}

Guo, Shuangping ^{[1
]}

Wilcox, Ryan A. ^{[7
]}

Teh, Bin Tean ^{[8
,9
]}

Lim, Soon Thye ^{[8
,9
]}

Tan, Soon Yong ^{[8
,9
]}

Rimsza, Lisa M. ^{[10
]}

Jaffe, Elaine S. ^{[11
]}

Campo, Elias ^{[12
]}

Martinez, Antonio ^{[12
]}

Delabie, Jan ^{[13
]}

Braziel, Rita M. ^{[14
]}

Cook, James R. ^{[15
]}

Tubbs, Raymond R. ^{[15
]}

Ott, German ^{[16
,17
]}

Geissinger, Eva ^{[3
]}

Gaulard, Philippe ^{[18
]}

Piccaluga, Pier Paolo ^{[19
]}

Pileri, Stefano A. ^{[19
]}

Au, Wing Y. ^{[20
]}

Nakamura, Shigeo ^{[21
]}

Seto, Masao ^{[21
]}

Berger, Francoise ^{[22
]}

de Leval, Laurence ^{[23
]}

Connors, Joseph M. ^{[4
]}

Armitage, James ^{[24
]}

Vose, Julie ^{[24
]}

Chan, Wing C. ^{[6
]}

Staudt, Louis M. ^{[2
]}

机构：

[1] Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

[2] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[3] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

[4] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada

[5] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA

[6] Univ Nebraska Med Ctr, Coll Publ Hlth, Dept Biostat, Omaha, NE USA

[7] Univ Michigan, Dept Internal Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[8] Natl Canc Ctr, Singapore, Singapore

[9] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore

[10] Univ Arizona, Dept Pathol, Tucson, AZ USA

[11] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[12] Univ Barcelona, Hosp Clin, Inst Invest Bomed August Pi & Sunyer, Barcelona, Spain

[13] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway

[14] Oregon Hlth & Sci Univ, Dept Clin Pathol, Portland, OR 97201 USA

[15] Cleveland Clin, Dept Mol Pathol & Lab Med, Cleveland, OH 44106 USA

[16] Robert Bosch Krankenhaus, Dept Clin Pathol, Stuttgart, Germany

[17] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany

[18] Univ Paris Est, Grp Henri Mondor Albert Chenevier, INSERM, Dept Pathol,U955, Creteil, France

[19] Univ Bologna, S Orsola Malpighi Hosp, Inst Hematol & Med Oncol L&A Seragnoli, Bologna, Italy

[20] Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China

[21] Aichi Canc Ctr, Nagoya, Aichi 464, Japan

[22] Ctr Hosp Lyon Sud, Lyon, France

[23] CHU Vaudois, Univ Inst Pathol, CH-1011 Lausanne, Switzerland

[24] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE USA

来源：

BLOOD | 2014年 / 123卷 / 19期

基金：

美国国家卫生研究院;

关键词：

DENDRITIC CELLS; IDENTIFICATION; DIFFERENTIATION; RECOGNITION; PREDICTION; PROFILES; EFFECTOR; SURVIVAL; FEATURES; SUBTYPES;

D O I：

10.1182/blood-2013-11-536359

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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).

引用

页码：2915 / 2923

页数：9

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