Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma.
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.
Iqbal
Javeed
J
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-3135, USA.
Weisenburger
Dennis D
DD
Greiner
Timothy C
TC
Vose
Julie M
JM
McKeithan
Timothy
T
Kucuk
Can
C
Geng
Huimin
H
Deffenbacher
Karen
K
Smith
Lynette
L
Dybkaer
Karen
K
Nakamura
Shigeo
S
Seto
Masao
M
Delabie
Jan
J
Berger
Francoise
F
Loong
Florence
F
Au
Wing Y
WY
Ko
Young-Hyeh
YH
Sng
Ivy
I
Armitage
James Olen
JO
Chan
Wing C
WC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002460:Cell Line; D002478:Cells, Cultured; D002648:Child; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000235:genetics; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D016399:Lymphoma, T-Cell / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D055815:Young Adult
C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases