RESUMO
Sézary syndrome (SS) represents 3% of cutaneous T-cell lymphomas (CTCL). It is an aggressive epidermotropic CTCL with a 5-year survival rate of 24%. According to EORTC (European organization for research and treatment of cancer), SS is defined by erythroderma, diffuse lymphadenopathy, atypical T lymphocytes (>1000/mm(3)), and the presence of a major blood, cutaneous and nodal T cell clone. A specific marker for atypical tumoral T lymphocytes known as Sézary cells was identified in 2001, namely KIR3DL2 (CD158k) receptor, which allows more specific diagnosis of SS; levels of this marker are highly correlated with the clinical course of the disease. In therapeutic terms, clinical trials are being conducted on new molecules that point towards an improved prognosis for this disease. We propose a review of Sézary syndrome, which is currently the subject of scientific papers concerning both physiopathology and therapeutics, with new prospects of targeted therapy.
Assuntos
Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Terapias em Estudo , Animais , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Bexaroteno , Biomarcadores Tumorais/análise , Terapia Combinada , Toxina Diftérica/uso terapêutico , Modelos Animais de Doenças , Elétrons/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Camundongos , Camundongos SCID , Terapia de Alvo Molecular , Terapia PUVA , Fotoferese , Receptores KIR3DL2/análise , Receptores KIR3DL2/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/patologia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Tetra-Hidronaftalenos/uso terapêuticoRESUMO
The molecular mechanisms regulating recruitment of intracellular signaling proteins like growth factor receptor-bound protein 2 (Grb2), phospholipase Cgamma1, or phosphatidylinositol 3-kinase (PI3-kinase) to the plasma membrane after stimulation of the T cell receptor (TCR)- CD3-zeta complex are not very well understood. We describe here purification, tandem mass spectrometry sequencing, molecular cloning, and biochemical characterization of a novel transmembrane adaptor protein which associates and comodulates with the TCR-CD3-zeta complex in human T lymphocytes and T cell lines. This protein was termed T cell receptor interacting molecule (TRIM). TRIM is a disulfide-linked homodimer which is comprised of a short extracellular domain of 8 amino acids, a 19-amino acid transmembrane region, and a 159-amino acid cytoplasmic tail. In its intracellular domain, TRIM contains several tyrosine-based signaling motifs that could be involved in SH2 domain-mediated protein-protein interactions. Indeed, after T cell activation, TRIM becomes rapidly phosphorylated on tyrosine residues and then associates with the 85-kD regulatory subunit of PI3-kinase via an YxxM motif. Thus, TRIM represents a TCR-associated transmembrane adaptor protein which is likely involved in targeting of intracellular signaling proteins to the plasma membrane after triggering of the TCR.