Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma

Javeed Iqbal, Dennis D. Weisenburger, Timothy Charles Greiner, Julie Marie Vose, Timothy McKeithan, Can Kucuk, Huimin Geng, Karen Deffenbacher, Lynette M Smith, Karen Dybkaer, Shigeo Nakamura, Masao Seto, Jan Delabie, Francoise Berger, Florence Loong, Wing Y. Au, Young Hyeh Ko, Ivy Sng, James Olen Armitage, Wing C. Chan

Research output: Contribution to journalArticle

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Abstract

Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL-not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK+ ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/ lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1-induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.

Original languageEnglish (US)
Pages (from-to)1026-1036
Number of pages11
JournalBlood
Volume115
Issue number5
DOIs
StatePublished - Feb 4 2010

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Peripheral T-Cell Lymphoma
T-cells
T-Cell Lymphoma
Anaplastic Large-Cell Lymphoma
Adult T Cell Leukemia Lymphoma
Follicular Dendritic Cells
Th17 Cells
Human T-lymphotropic virus 1
Cytotoxic T-Lymphocytes
Gene Expression Profiling
Immunosuppressive Agents
Natural Killer Cells
Cell Biology
Cell Differentiation
Lymphoma
Neoplasms
B-Lymphocytes
Cytokines
Tumors
Classifiers

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. / Iqbal, Javeed; Weisenburger, Dennis D.; Greiner, Timothy Charles; Vose, Julie Marie; McKeithan, Timothy; Kucuk, Can; Geng, Huimin; Deffenbacher, Karen; Smith, Lynette M; Dybkaer, Karen; Nakamura, Shigeo; Seto, Masao; Delabie, Jan; Berger, Francoise; Loong, Florence; Au, Wing Y.; Ko, Young Hyeh; Sng, Ivy; Armitage, James Olen; Chan, Wing C.

In: Blood, Vol. 115, No. 5, 04.02.2010, p. 1026-1036.

Research output: Contribution to journalArticle

Iqbal, J, Weisenburger, DD, Greiner, TC, Vose, JM, McKeithan, T, Kucuk, C, Geng, H, Deffenbacher, K, Smith, LM, Dybkaer, K, Nakamura, S, Seto, M, Delabie, J, Berger, F, Loong, F, Au, WY, Ko, YH, Sng, I, Armitage, JO & Chan, WC 2010, 'Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma', Blood, vol. 115, no. 5, pp. 1026-1036. https://doi.org/10.1182/blood-2009-06-227579
Iqbal, Javeed ; Weisenburger, Dennis D. ; Greiner, Timothy Charles ; Vose, Julie Marie ; McKeithan, Timothy ; Kucuk, Can ; Geng, Huimin ; Deffenbacher, Karen ; Smith, Lynette M ; Dybkaer, Karen ; Nakamura, Shigeo ; Seto, Masao ; Delabie, Jan ; Berger, Francoise ; Loong, Florence ; Au, Wing Y. ; Ko, Young Hyeh ; Sng, Ivy ; Armitage, James Olen ; Chan, Wing C. / Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma. In: Blood. 2010 ; Vol. 115, No. 5. pp. 1026-1036.
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AU - Iqbal, Javeed

AU - Weisenburger, Dennis D.

AU - Greiner, Timothy Charles

AU - Vose, Julie Marie

AU - McKeithan, Timothy

AU - Kucuk, Can

AU - Geng, Huimin

AU - Deffenbacher, Karen

AU - Smith, Lynette M

AU - Dybkaer, Karen

AU - Nakamura, Shigeo

AU - Seto, Masao

AU - Delabie, Jan

AU - Berger, Francoise

AU - Loong, Florence

AU - Au, Wing Y.

AU - Ko, Young Hyeh

AU - Sng, Ivy

AU - Armitage, James Olen

AU - Chan, Wing C.

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N2 - Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Gene expression profiling was performed on 144 cases of PTCL and natural killer cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL), and adult T-cell leukemia/lymphoma. PTCL-unclassifiable was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T lymphocytes and a poor survival compared with the remaining PTCL-not otherwise specified cases. Many of the pathologic features and substantial components of the molecular signature of AITL are contributed by the follicular dendritic cells, B-cell, and other stromal components. The expression of Th17-associated molecules in ALK+ ALCL was noted and may represent aberrant activation of Th17-cell differentiation by abnormal cytokine secretion. Adult T-cell leukemia/ lymphoma has a homogeneous molecular signature demonstrating high expression of human T-lymphotropic virus type 1-induced genes. These classifiers reflect the biology of the tumor cells as well as their microenvironment. We also constructed a molecular prognosticator for AITL that appears to be largely related to the microenvironmental signature, and the high expression of 2 immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions also were identified, and these findings may lead to better therapies and outcome in the future.

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