Molecular etiology of mature T-cell non-hodgkins lymphomas

Abstract

T-cell non-Hodgkin's lymphomas (NHL) represent approximately 10-15% of all lymphomas diagnosed in Western countries. Significant progress has been made over the last 2 decades in defining non-random chromosomal abnormalities. Cytogenetic and molecular analyses have enhanced diagnostic capabilities as well as improved classification and prognostication for T-cell NHL. Gamma-delta T-cell receptor (TCR) clonality now represents the more common TCR rearrangement in subcutaneous panniculitis-like T-cell lymphoma (SCPTCL), hepatosplenic T-cell lymphoma (HSTCL), extranodal NK/T-cell lymphoma, nasal type and enteropathy-type intestinal T-cell lymphoma (EITCL). Non-random, recurrent chromosome abnormalities such as isochrome 7 with HSTCL, complex karyotypes with peripheral T-cell lymphoma, not otherwise characterized (PTCL-NOC), trisomies 3 and 5 with angioimmunoblastic lymphoma (AIL) and t(2;5) with systemic anaplastic T-cell lymphoma have been recognized. Furthermore, identification of relevant protooncogenes and tumor suppressor genes involved in the pathogenesis of T-cell NHL such as the NPM/ALK fusion protein, p53, cyclin dependent kinase inhibitors (p15, p16, p21) and EBV as well as their interplay with the various regulatory pathways of cell cycle progression and apoptosis represent potential candidates for molecular-based therapy. This review presents a detailed analysis of the molecular and genetic perturbations present in mature T-cell lymphomas including discussion of how tumor-specific alterations impact on clinical outcome. Future studies in T-cell NHL are likely to provide additional disease-specific chromosomal translocations and molecular alterations with important translational implications.

Inactivation of the p16 Cyclin-Dependent Kinase Inhibitor in High-Grade Canine Non-Hodgkin's T-Cell Lymphoma

“…2,5 Hence, it has been hypothesized that inactivation of the p16 inhibitor of CDK4 and CDK6 (Ink4-a, Cdkn2, Mts-1) is an important factor in the pathogenesis of T-cell lymphoproliferative diseases. 5,11,28 Experimental evidence supports this hypothesis in human T-cell leukemias, especially in pediatric patients; 4,6,29,30 in addition, viral-induced lymphomagenesis in people infected by the human T-lymphotropic virus-I (HTLV-1) may be at least partly due to the inactivation of p16 by HTLV-1 Tax protein. 40 Nevertheless, these findings are confounded by the fact that overlapping reading frames encode another tumor Vet Pathol 44:467-478 (2007) suppressor gene within the INK4 locus (called Arf; p19 in humans and p14 in mice).…”

Treatment of T-cell non-hodgkin’ lymphoma

“…Gamma-delta TCR clonality represents the more common TCR rearrangement in SCPTCL, HSTCL, extranodal NK/T-cell lymphoma nasal type, and EITCL. Nonrandom recurrent chromosome abnormalities, such as isochrome 7 with HSTCL, complex karyotypes with PTCL-noc, trisomies 3 and 5 with AIL, and t(2;5) with systemic anaplastic T-cell lymphoma, have been recognized [13]. The molecular etiology of T-cell NHL was reviewed by Evens and Gartenhaus [13].…”

T-cell non-Hodgkin lymphoma

“…Tax, a potent HTLV-1 transcription activator, plays an important role in HTLV-1-induced transformation and resistance to apoptosis, in part through the activation of the NF-B pathway. 12 Adult T-cell leukemia cells often express CD3, CD4, CD25, and CD52 antigens.…”