Molecular classification of T-cell lymphomas

Leval, Laurence de; Bisig, Bettina; Thielen, Caroline; Boniver, Jacques; Gaulard, Philippe

doi:10.1016/j.critrevonc.2009.01.002

Cited by 68 publications

(56 citation statements)

References 103 publications

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“…For such cases, gene expression profiling may be very helpful in the future for confirming the correct diagnosis. [24][25][26][27] The clinical features of our patients with PTCL-NOS are similar to those reported by other studies. [5][6][7][8][9][10][11][12][13]20,23,28 The median age of our patients was 60 years (range, 19-87 years), with a male predominance, and the majority of the patients (69%) presented with advanced stage disease.…”

supporting

confidence: 79%

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

Weisenburger

Savage

Harris

et al. 2011

Blood

387

354

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The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was toanalyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (> 10 cm), thrombocytopenia (< 150 ؋ 10 9 /L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies. (Blood. 2011;117(12):3402-3408) IntroductionPeripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are an uncommon and heterogeneous group of disorders that compose 5% to 20% of all non-Hodgkin lymphomas (NHLs) in different parts of the world. 1,2 In recent years, the incidence of PTCL and NKTCL in the United States has increased by almost 3-fold with an annual increase of 3.8%, whereas the incidence of B-cell lymphoma and Hodgkin lymphoma has been relatively stable. 3,4 One of the most common subtypes of PTCL is a heterogeneous group of nodal and extranodal mature T-cell lymphomas that do not correspond to any of the specifically defined T-cell entities in the World Health Organization classification, 1 and are therefore called PTCL, not otherwise specified (NOS). Uncommon variants of PTCL-NOS include lymphoepithelioid (Lennert) lymphoma, and cases with a follicular or T-zone pattern of growth. 1 Over the last 12 years, several clinical studies have attempted to identify the clinical and pathologic features of prognostic importance in PTCL-NOS, but the number of cases in these studies was generally small and the findings have been inconsistent or unconfirmed. [5][6][7][8][9][10][11][12][13] The International Peripheral T-cell Lymphoma Project was undertaken as a large retrospective study of PTCL and NKTCL in North America, Europe, and Asia with the goal of better characterizing this group of NHL. One objective of was to analyze the clinical and pathologic features of the 340 cases of PTCL-NOS in the study, and to determine the important prognostic factors for this uncommon entity. MethodsTwenty-two institutions in North America, Europe, and Asia partici...

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supporting

confidence: 79%

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

Weisenburger

Savage

Harris

et al. 2011

Blood

387

354

View full text Add to dashboard Cite

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“…10 Interestingly, this is also in line with genome-wide expression profiling studies in which fairly similar molecular signatures and pathways have been found for systemic ALCL irrespective of ALK gene rearrangements, [11][12][13] while few differences have been found between cutaneous and systemic cases of ALCL. 14 In particular, the level of similarity observed between the neoplastic cells in systemic ALKnegative ALCL and primary cutaneous CD30 + lymphoproliferations is noteworthy as these conditions usually have clearly different clinical presenting features and evolution.…”

supporting

confidence: 65%

“…[8][9][10] Based on the above studies, current international guidelines continue to recommend the use of fluconazole until engraftment in patients who have undergone allogeneic HSCT, and, for the first time, recommend the use of a broad spectrum drug, oral posaconazole, during intensive immunosuppressive therapy for graft-versus-host disease, and in patients with acute myeloid leukemia or myelodysplastic syndromes during remission induction chemotherapy. [11][12][13] These recommendations reflect important progresses obtained in the prevention of invasive fungal infections, including those caused by filamentous fungi, but they have been unable to generate a consensus on the optimal prophylaxis of invasive fungal infections in the complex scenario of hematologic disorders, particularly in the transplant setting. This problem has been underlined in a recent consensus process by the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) which observed that key recommendations by international guidelines imply various problems such as the lack of any approved mold-active prophylaxis during the engraftment phase in allogeneic HSCT, and the lack of an intravenous formulation of posaconazole, which could limit the use of this drug in patients unable to tolerate oral medications or with altered intestinal absorption.…”

mentioning

confidence: 99%

CD30+ lymphoproliferative disorders

Leval¹,

Gaulard²

2010

Haematologica

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“…Blockade of TCR signaling may be therapeutically useful in peripheral lymphomas. Mature PTCLs are diverse morphologically but similar in that the majority express TCR and carry an extremely poor prognosis (44,45,67). Treatment options for these cancers are limited and tend to be ineffective.…”

Section: Discussionmentioning

confidence: 99%

TCR-dependent transformation of mature memory phenotype T cells in mice

Wang

Werneck²,

Wilson³

et al. 2011

J. Clin. Invest.

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A fundamental goal in cancer research is the identification of the cell types and signaling pathways capable of initiating and sustaining tumor growth, as this has the potential to reveal therapeutic targets. Stem and progenitor cells have been implicated in the genesis of select lymphoid malignancies. However, the identity of the cells in which mature lymphoid neoplasms are initiated remains unclear. Here, we investigate the origin of peripheral T cell lymphomas using mice in which Snf5, a chromatin remodelling-complex subunit with tumor suppressor activity, could be conditionally inactivated in developing T cells. In this model of mature peripheral T cell lymphomas, the cell of origin was a mature CD44 hi CD122 lo CD8 + T cell that resembled a subset of memory cells that has capacity for self-renewal and robust expansion, features shared with stem cells. Further analysis showed that Snf5 loss led to activation of a Myc-driven signaling network and stem cell transcriptional program. Finally, lymphomagenesis and lymphoma proliferation depended upon TCR signaling, establishing what we believe to be a new paradigm for lymphoid malignancy growth. These findings suggest that the selfrenewal and robust proliferative capacities of memory T cells are associated with vulnerability to oncogenic transformation. Our findings further suggest that agents that impinge upon TCR signaling may represent an effective therapeutic modality for this class of lethal human cancers.

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Molecular classification of T-cell lymphomas

Cited by 68 publications

References 103 publications

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

Peripheral T-cell lymphoma, not otherwise specified: a report of 340 cases from the International Peripheral T-cell Lymphoma Project

CD30+ lymphoproliferative disorders

TCR-dependent transformation of mature memory phenotype T cells in mice

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