RESUMO
While mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP-1, heat-shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP-depending RNA helicase (DDX17) and the α-isoform of lamina-associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non-aggressive. Moreover, PARP-1 was overexpressed in patients with early stage of MF who developed later an aggressive disease. PARP-1 was evaluated as a new target for therapy, demonstrating the selective dose-dependent cytotoxic effect of PARP inhibitors on Sézary cells in comparison with non-malignant lymphocytes. In conclusion, we believe that PARP-1 may serve not only as a biomarker at initial biopsies for a disease that may become aggressive but also as a new therapeutic target of advanced MF and Sézary syndrome.
Assuntos
Micose Fungoide/diagnóstico , Poli(ADP-Ribose) Polimerase-1/metabolismo , Síndrome de Sézary/diagnóstico , Biomarcadores , Biópsia , Óxidos N-Cíclicos/metabolismo , Progressão da Doença , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Linfócitos/metabolismo , Micose Fungoide/metabolismo , Estadiamento de Neoplasias , Proteômica , Estudos Retrospectivos , Fatores de Risco , Síndrome de Sézary/metabolismo , Neoplasias Cutâneas/metabolismoAssuntos
Biomarcadores Tumorais/análise , Subunidade p35 da Interleucina-12/análise , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/diagnóstico , Células Dendríticas/química , Derme/patologia , Eczema/patologia , Feminino , Humanos , Lactente , Células de Langerhans/química , Masculino , Pessoa de Meia-Idade , Micose Fungoide/química , Micose Fungoide/patologia , Psoríase/patologia , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologia , Microambiente TumoralRESUMO
Romidepsin belongs to a class of medications called histone deacetylase inhibitors and is currently approved for treatment of cutaneous and peripheral T-cell lymphomas. Romidepsin was previously investigated for the treatment of chronic lymphocytic leukemia (CLL), and demonstrated potential benefit, but interest in its use declined following phase I clinical trials that showed poor tolerance of a significant side effect profile. We presented a patient with a history of stage II CLL, referred to dermatology for treatment of new-onset of mycosis fungoides (MF), who was treated with romidepsin over seven months. The patient achieved a partial response with 50% decrease in body surface area occupied by MF, thinning of remaining plaques, and near complete response in his CLL. His absolute lymphocyte count remained within the normal range for four months following discontinuation of romidepsin. Side effects were well-tolerated and did not limit therapy. Current literature on romidepsin is reviewed and compared to existing treatments for CLL.