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

Javeed Iqbal, Dennis D Weisenburger, Timothy C Greiner, Julie M Vose, Timothy McKeithan, Can Kucuk, Huimin Geng, Karen Deffenbacher, Lynette 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 journalJournal articleResearchpeer-review

332 Citations (Scopus)

Abstract

Peripheral T-cell lymphoma (PTCL) is often challenging to diagnose and classify. Since most patients also have a poor outcome with standard chemotherapy, a better understanding of PTCL may lead to more effective diagnosis and therapy. Gene expression profiling (GEP) was performed on 144 cases of PTCL and natural killer (NK)-cell lymphoma and robust molecular classifiers were constructed for angioimmunoblastic T-cell lymphoma (AITL), ALK positive anaplastic large cell lymphoma (ALK+ALCL), and adult T-cell leukemia/lymphoma (ATLL). PTCL-Unclassifiable (PTCL-U) was molecularly heterogeneous, but we were able to identify a molecular subgroup with features of cytotoxic T- lymphocytes and a poor survival compared to the remaining PTCL-U cases. Many of the pathological 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. ATLL has a homogeneous molecular signature showing high expression of HTLV-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 which appears to be largely related to the microenvironmental signature and the high expression of two immunosuppressive signatures are associated with poor outcome. Oncogenic pathways and tumor-host interactions were also identified and these findings may lead to better therapies and outcome in the future.
Original languageEnglish
JournalBlood
Volume115
Pages (from-to)1026-1036
Number of pages11
ISSN0006-4971
DOIs
Publication statusPublished - 2010
Externally publishedYes

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