Peripheral T cell lymphoma, unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and poor prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T cells. Comparison with the profiles of purified T cell subpopulations (CD4+, CD8+, resting [HLA-DR–], and activated [HLA-DR+]) reveals that PTCLs/U are most closely related to activated peripheral T lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g., apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic, or stromal location. PTCLs/U aberrantly express, among others, PDGFRα, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRα and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone deacetylase) were found. These results, which might be extended to other more rare PTCL categories, provide insight into tumor pathogenesis and clinical management of PTCL/U.
Pier Paolo Piccaluga, Claudio Agostinelli, Andrea Califano, Maura Rossi, Katia Basso, Simonetta Zupo, Philip Went, Ulf Klein, Pier Luigi Zinzani, Michele Baccarani, Riccardo Dalla Favera, Stefano A. Pileri
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International Journal of Hematology | 2014 |
A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma.
Yoo HY, Sung MK, Lee SH, Kim S, Lee H, Park S, Kim SC, Lee B, Rho K, Lee JE, Cho KH, Kim W, Ju H, Kim J, Kim SJ, Kim WS, Lee S, Ko YH |
Nature Genetics | 2014 |
Mature T-cell Lymphomagenesis Induced by Retroviral Insertional Activation of Janus Kinase 1
T Heinrich, B Rengstl, A Muik, M Petkova, F Schmid, R Wistinghausen, K Warner, G Crispatzu, ML Hansmann, M Herling, D Laer, S Newrzela |
Molecular Therapy | 2013 |
microRNA expression profiling identifies molecular signatures associated with anaplastic large cell lymphoma
C Liu, J Iqbal, J Teruya-Feldstein, Y Shen, MJ Dabrowska, K Dybkaer, MS Lim, R Piva, A Barreca, E Pellegrino, E Spaccarotella, CM Lachel, C Kucuk, CS Jiang, X Hu, S Bhagavathi, TC Greiner, DD Weisenburger, P Aoun, SL Perkins, TW McKeithan, G Inghirami, WC Chan |
Blood | 2013 |
Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis
TK Das, D Dana, SS Paroly, SK Perumal, S Singh, H Jhun, J Pendse, RL Cagan, TT Talele, S Kumar |
Oncogenesis | 2013 |
Peripheral T-cell lymphomas: a review of current approaches and hopes for the future
AP Skarbnik, M Burki, B Pro |
Frontiers in Oncology | 2013 |
CD30-positive peripheral T-cell lymphomas share molecular and phenotypic features
B Bisig, A Reyniès, C Bonnet, P Sujobert, DS Rickman, T Marafioti, G Delsol, L Lamant, P Gaulard, L Leval |
Haematologica | 2013 |
Truncated Form of TGF-βRII, But Not Its Absence, Induces Memory CD8 + T Cell Expansion and Lymphoproliferative Disorder in Mice
H Ishigame, MM Mosaheb, S Sanjabi, RA Flavell |
Journal of immunology (Baltimore, Md. : 1950) | 2013 |
New molecular insights into peripheral T cell lymphomas
Stefano Pileri, Pier Paolo Piccaluga |
Journal of Clinical Investigation | 2012 |
Molecular Profiling of Aggressive Lymphomas
M Rossi, MA Laginestra, A Gazzola, MR Sapienza, SA Pileri, PP Piccaluga |
Advances in Hematology | 2012 |
Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets
M Travert, Y Huang, L Leval, N Martin-Garcia, MH Delfau-Larue, F Berger, J Bosq, J Briere, J Soulier, E MacIntyre, T Marafioti, A Reynies, P Gaulard |
Blood | 2012 |
PDGFR blockade is a rational and effective therapy for NPM-ALK–driven lymphomas
D Laimer, H Dolznig, K Kollmann, PW Vesely, M Schlederer, O Merkel, AI Schiefer, MR Hassler, S Heider, L Amenitsch, C Thallinger, PB Staber, I Simonitsch-Klupp, M Artaker, S Lagger, SD Turner, S Pileri, PP Piccaluga, P Valent, K Messana, I Landra, T Weichhart, S Knapp, M Shehata, M Todaro, V Sexl, G Höfler, R Piva, E Medico, BA Ruggeri, M Cheng, R Eferl, G Egger, JM Penninger, U Jaeger, R Moriggl, G Inghirami, L Kenner |
Nature Medicine | 2012 |
Identification of multiple subclones in peripheral T-cell lymphoma, not otherwise specified with genomic aberrations
N Yoshida, A Umino, F Liu, K Arita, K Karube, S Tsuzuki, K Ohshima, M Seto |
Cancer Medicine | 2012 |
An integrated genome-wide approach to discover tumor-specific antigens as potential immunologic and clinical targets in cancer
QW Xu, W Zhao, Y Wang, MA Sartor, DM Han, J Deng, R Ponnala, JY Yang, QY Zhang, GQ Liao, YM Qu, L Li, FF Liu, HM Zhao, YH Yin, WF Chen, Y Zhang, XS Wang |
Cancer research | 2012 |
Genetic alterations in systemic nodal and extranodal non‐cutaneous lymphomas derived from mature T cells and natural killer cells
Boi M, Stathis A, Zucca E, Inghirami G, Bertoni F |
Cancer Science | 2012 |
T cell receptor dependent transformation of mature memory phenotype T cells in mice
Xi Wang, Miriam Werneck, Boris Wilson, Hye-Jung Kim, Michael Kluk, Christopher Thom, Jonathan Wischhusen, Julia Evans, Jonathan Jesneck, Phuong Nguyen, Courtney Sansam, Harvey Cantor, Charles Roberts |
Journal of Clinical Investigation | 2011 |
Identification and Characterization of Peripheral T-Cell Lymphoma-Associated SEREX Antigens
CD Cooper, CH Lawrie, AP Liggins, GP Collins, CS Hatton, K Pulford, AH Banham |
PloS one | 2011 |
Extranodal NK/T-cell lymphoma: toward the identification of clinical molecular targets
C Schmitt, N Sako, M Bagot, Y Huang, P Gaulard, A Bensussan |
Journal of biomedicine & biotechnology | 2011 |
Activation of T-cell receptor signaling in peripheral T-cell lymphoma cells plays an important role in the development of lymphoma-associated hemophagocytosis
J An, H Fujiwara, K Suemori, T Niiya, T Azuma, K Tanimoto, T Ochi, Y Akatsuka, J Mineno, H Ozawa, F Ishikawa, K Kuzushima, M Yasukawa |
International Journal of Hematology | 2011 |
The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications
E Campo, SH Swerdlow, NL Harris, S Pileri, H Stein, ES Jaffe |
Blood | 2011 |
Pathobiology of ALK-negative anaplastic large cell lymphoma
SA Pileri, C Agostinelli, F Bacci, E Sabattini, C Sagramoso, B Falini, PP Piccaluga |
Pediatric reports | 2011 |
Pathobiology of anaplastic large cell lymphoma
PP Piccaluga, A Gazzola, C Mannu, C Agostinelli, F Bacci, E Sabattini, C Sagramoso, R Piva, F Roncolato, G Inghirami, SA Pileri |
Advances in Hematology | 2010 |
Rapid Remission in Peripheral T-Cell Lymphoma of the Nasal Type by the Bortezomib plus CHOP Therapy
LJ Xue, XB Mao, XB Liu, QS Su, HJ Yu, JH Yang |
Case Reports in Medicine | 2010 |
Prognostic markers in peripheral T-cell lymphoma
PP Piccaluga, C Agostinelli, A Gazzola, C Mannu, F Bacci, E Sabattini, SA Pileri |
Current Hematologic Malignancy Reports | 2010 |
Mast cells and Th17 cells contribute to the lymphoma-associated pro-inflammatory microenvironment of angioimmunoblastic T-cell lymphoma
C Tripodo, G Gri, PP Piccaluga, B Frossi, C Guarnotta, S Piconese, G Franco, V Vetri, CE Pucillo, AM Florena, MP Colombo, SA Pileri |
The American Journal of Pathology | 2010 |
The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma
K Pechloff, J Holch, U Ferch, M Schweneker, K Brunner, M Kremer, T Sparwasser, L Quintanilla-Martinez, U Zimber-Strobl, B Streubel, A Gewies, C Peschel, J Ruland |
Journal of Experimental Medicine | 2010 |
Peripheral T cell lymphoma: new model + new insight
JC Mulloy |
Journal of Experimental Medicine | 2010 |
New Strategies in Peripheral T-cell lymphoma: Understanding Tumor Biology and Developing Novel Therapies
K Dunleavy, RL Piekarz, J Zain, JE Janik, WH Wilson, OA O'Connor, SE Bates |
Clinical cancer research | 2010 |
Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas
PP Piccaluga, M Navari, GD Falco, MR Ambrosio, S Lazzi, F Fuligni, C Bellan, M Rossi, MR Sapienza, MA Laginestra, M Etebari, EA Rogena, L Tumwine, C Tripodo, D Gibellini, J Consiglio, CM Croce, SA Pileri, L Leoncini |
Oncotarget | 2010 |
Molecular signatures to improve diagnosis in peripheral T-cell lymphoma and prognostication in angioimmunoblastic T-cell lymphoma
Iqbal J, Weisenburger DD, Greiner TC, Vose JM, McKeithan T, Kucuk C, Geng H, Deffenbacher K, Smith L, Dybkaer K, Nakamura S, Seto M, Delabie J, Berger F, Loong F, Au WY, Ko YH, Sng I, Armitage JO, Chan WC |
Blood | 2010 |
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd |
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type
Y Huang, A Reyniès, L Leval, B Ghazi, N Martin-Garcia, M Travert, J Bosq, J Brière, B Petit, E Thomas, P Coppo, T Marafioti, JF Emile, MH Delfau-Larue, C Schmitt, P Gaulard |
Blood | 2009 |
Physiological PTEN expression in peripheral T-cell lymphoma not otherwise specified
A Gazzola, C Bertuzzi, C Agostinelli, S Righi, SA Pileri, PP Piccaluga |
Haematologica | 2009 |
Peripheral T-cell Lymphomas With a Follicular Growth Pattern are Derived From Follicular Helper T Cells (TFH) and may Show Overlapping Features With Angioimmunoblastic T-cell Lymphomas:
Y Huang, A Moreau, J Dupuis, B Streubel, B Petit, SL Gouill, N Martin-Garcia, C Copie-Bergman, F Gaillard, M Qubaja, B Fabiani, G Roncador, C Haioun, MH Delfau-Larue, T Marafioti, A Chott, P Gaulard |
The American Journal of Surgical Pathology | 2009 |
Update on the World Health Organization classification of peripheral T-cell lymphomas.
O'Leary HM, Savage KJ |
Current Hematologic Malignancy Reports | 2009 |
Gamma-delta T-cell lymphomas.
Tripodo C, Iannitto E, Florena AM, Pucillo CE, Piccaluga PP, Franco V, Pileri SA |
Nature reviews. Clinical oncology | 2009 |
Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications
WJ Chng, ED Remstein, R Fonseca, PL Bergsagel, JA Vrana, PJ Kurtin, A Dogan |
Blood | 2008 |
Peripheral T cell lymphoma, not otherwise specified: the stuff of genes, dreams and therapies
C Agostinelli, PP Piccaluga, P Went, M Rossi, A Gazzola, S Righi, T Sista, C Campidelli, PL Zinzani, B Falini, SA Pileri |
Journal of clinical pathology | 2008 |