title: Peripheral T-cell and NK cell lymphoproliferative disorders: cell of origin, clinical and pathological implications.
abstract: T-cell lymphoproliferative disorders are a heterogeneous group of neoplasms with distinct clinical-biological properties. The normal cellular counterpart of these processes has been postulated based on functional and immunophenotypic analyses. However, T lymphocytes have been proven to be remarkably capable of modulating their properties, adapting their function in relationship with multiple stimuli and to the microenvironment. This impressive plasticity is determined by the equilibrium among a pool of transcription factors and by DNA chromatin regulators. It is now proven that the acquisition of specific genomic defects leads to the enforcement/activation of distinct pathways, which ultimately alter the preferential activation of defined regulators, forcing the neoplastic cells to acquire features and phenotypes distant from their original fate. Thus, dissecting the landscape of the genetic defects and their functional consequences in T-cell neoplasms is critical not only to pinpoint the origin of these tumors but also to define innovative mechanisms to re-adjust an unbalanced state to which the tumor cells have become addicted and make them vulnerable to therapies and targetable by the immune system. In our review, we briefly describe the pathological and clinical aspects of the T-cell lymphoma subtypes as well as NK-cell lymphomas and then focus on the current understanding of their pathogenesis and the implications on diagnosis and treatment.
authors.affiliation: Department of Molecular Biotechnology and Health Science and Center for Experimental Research and Medical Studies (CeRMS), University of Torino, Torino, Italy; Department of Pathology, and NYU Cancer Center, New York University School of Medicine, New York, NY, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Stefano
authors.initials: S
authors.lastname: Pileri
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D042002:Chromatin Assembly and Disassembly / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D054391:Lymphoma, Extranodal NK-T-Cell / Q000276:immunology*; D016411:Lymphoma, T-Cell, Peripheral / Q000276:immunology*; D014411:Neoplastic Stem Cells / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014157:Transcription Factors
keywords: T-cell lymphoma; cell of origin; mechanisms of transformation