TY - JOUR
T1 - Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma
AU - Iqbal, Javeed
AU - Weisenburger, Dennis D
AU - Greiner, Timothy C
AU - Vose, Julie M
AU - McKeithan, Timothy
AU - Kucuk, Can
AU - Geng, Huimin
AU - Deffenbacher, Karen
AU - Smith, Lynette
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
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1182/blood-2009-06-227579
DO - 10.1182/blood-2009-06-227579
M3 - Journal article
SN - 0006-4971
VL - 115
SP - 1026
EP - 1036
JO - Blood
JF - Blood
ER -