RESUMO
Comparison of the 2007 EORTC/ISCL and the 2022 EORTC/ISCL/USCLC blood staging guidelines for cutaneous T-cell lymphoma at a single institution reveals the newer guidelines fail to detect a subset of patients with Sézary syndrome with low blood burden.
Assuntos
Linfoma Cutâneo de Células T , Estadiamento de Neoplasias , Síndrome de Sézary , Neoplasias Cutâneas , Humanos , Síndrome de Sézary/patologia , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/sangue , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/sangue , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Infections are one of the major causes of death in patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS). However, few recent data are available on the characteristics and risk factors of these infectious events. OBJECTIVES: To describe infectious events occurring in a cohort of patients with MF/SS, and to identify associated clinical and biological risk factors. METHODS: A retrospective cohort study was performed to investigate infectious events and associated factors in patients diagnosed with MF (stage IB and beyond) or SS followed from May 2011 to May 2016 at the University Hospital of Bordeaux, France. RESULTS: Seventy-one patients with complete follow-up were included. Eighty infectious events were recorded in 40 patients, including 28 skin and soft tissue infections and 25 cases of pneumonia. Opportunistic infections, which are usually associated with depleted cell-mediated immunity, were scarce (9%). In multivariate analysis, cardiac, renal or lung comorbidities [odds ratio (OR) 7·2, 95% confidence interval (CI) 3·3-15·9; P = 0·002], SS (OR 8·8, 95% CI 7·7-10·2; P = 0·037) and lymphocyte count < 0·5 × 109 cells L-1 (OR 6·4, 95% CI 1·5-27·4; P = 0·004) were significantly associated with a higher risk of infection. CONCLUSIONS: Opportunistic germs were rarely recorded, but their incidence was probably prevented by adequate prophylaxis (ongoing in 28% of patients). As in patients living with AIDS, pneumonias were frequent. On the other hand, bacterial cutaneous infections represent a specific pattern in patients with MF/SS. Patients with chronic organ failure, lymphocytopenia and SS should be considered as being at high risk for infectious events. Pneumococcal vaccination should be systematically recommended, and prophylaxis with co-trimoxazole and valaciclovir when the CD4 count is < 0·2 × 109 cells L-1 .
Assuntos
Micose Fungoide/complicações , Infecções Oportunistas/epidemiologia , Pneumonia/epidemiologia , Síndrome de Sézary/complicações , Dermatopatias Infecciosas/epidemiologia , Neoplasias Cutâneas/complicações , Comorbidade , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/epidemiologia , Micose Fungoide/imunologia , Estadiamento de Neoplasias , Infecções Oportunistas/imunologia , Pneumonia/imunologia , Estudos Retrospectivos , Fatores de Risco , Síndrome de Sézary/sangue , Síndrome de Sézary/epidemiologia , Síndrome de Sézary/imunologia , Dermatopatias Infecciosas/imunologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/imunologiaRESUMO
The practice of pre-emptive individualized medicine is predicated on the discovery, development and application of biomarkers in specific clinical settings. Mycosis fungoides and Sézary syndrome are the two most common type of cutaneous T-cell lymphoma, yet diagnosis, prognosis and disease monitoring remain a challenge. In this review, we discuss the current state of biomarker discovery in mycosis fungoides and Sézary syndrome, highlighting the most promising molecules in different compartments. Further, we emphasize the need for continued multicentre efforts to validate available and new biomarkers and to develop prospective combinatorial panels of already discovered molecules.
Assuntos
Biomarcadores/sangue , Micose Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Expressão Gênica , Humanos , Micose Fungoide/sangue , Síndrome de Sézary/sangueRESUMO
BACKGROUND: Sézary syndrome (SS) is characterized by erythroderma with leukemic involvement. In atypical SS, leukemic involvement is present without erythroderma. Little is known about the presentation, prognosis, and outcome in these patients. OBJECTIVE: We sought to describe our experience with patients with SS without erythroderma. METHODS: We retrospectively identified patients with SS, but without erythroderma, at Mayo Clinic from 1976 to 2010. Patients all met criteria for high blood tumor burden. Their clinical characteristics, disease course, and prognosis were reviewed and compared with a previously described cohort of 176 patients with SS from this institution. RESULTS: Among 16 patients identified, all had cutaneous findings consistent with cutaneous T-cell lymphoma, most commonly erythematous patches (n = 6) and plaques (n = 12). All 16 patients were deceased at the time of the study. Median time from diagnosis of SS without erythroderma to the date of death was 3.6 years (range, 0.5-8.7 years). Survival was not different between patients with SS with and without erythroderma (hazard ratio 1.58; 95% confidence interval 0.94-2.66; P = .08). LIMITATIONS: This was a single-institution retrospective study. CONCLUSION: Leukemic involvement may confer shortened survival in patients with SS, because the presence of erythroderma did not affect survival. These atypical cases could potentially be more accurately described using the TNMB classification.
Assuntos
Dermatite Esfoliativa , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Idoso , Biópsia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Infiltração Leucêmica , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Especificidade de Órgãos , Prognóstico , Estudos Retrospectivos , Síndrome de Sézary/sangue , Síndrome de Sézary/classificação , Síndrome de Sézary/diagnóstico , Pele/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/diagnóstico , Avaliação de Sintomas , Carga TumoralRESUMO
BACKGROUND: Accurate quantification of malignant cells in the peripheral blood of patients with cutaneous T-cell lymphoma is important for early detection, prognosis, and monitoring disease burden. OBJECTIVE: We sought to determine the spectrum of current clinical practices; critically evaluate elements of current International Society for Cutaneous Lymphomas (ISCL) B1 and B2 staging criteria; and assess the potential role of T-cell receptor-Vß analysis by flow cytometry. METHODS: We assessed current clinical practices by survey, and performed a retrospective analysis of 161 patients evaluated at Yale (2011-2014) to compare the sensitivity, specificity, positive predictive value, and negative predictive value of parameters for ISCL B2 staging. RESULTS: There was heterogeneity in clinical practices among institutions. ISCL B1 criteria did not capture 5 Yale cohort cases with immunophenotypic abnormalities that later progressed. T-cell receptor-Vß testing was more specific than polymerase chain reaction and aided diagnosis in detecting clonality, but was of limited benefit in quantification of tumor burden. LIMITATIONS: Because of limited follow-up involving a single center, further investigation will be necessary to conclude whether our proposed diagnostic algorithm is of general clinical benefit. CONCLUSION: We propose further study of modified B1 criteria: CD4/CD8 ratio 5 or greater, %CD4(+) CD26(-) 20% or greater, or %CD4(+) CD7(-) 20% or greater, with evidence of clonality. T-cell receptor-Vß testing should be considered in future diagnostic and staging algorithms.
Assuntos
Linfoma Cutâneo de Células T/sangue , Linfoma Cutâneo de Células T/patologia , Receptores de Antígenos de Linfócitos T/imunologia , Neoplasias Cutâneas/sangue , Adulto , Idoso , Estudos Transversais , Feminino , Citometria de Fluxo/métodos , Testes Hematológicos , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/patologia , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase/métodos , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Doenças Raras , Estudos Retrospectivos , Síndrome de Sézary/sangue , Síndrome de Sézary/patologia , Neoplasias Cutâneas/patologia , Sociedades Médicas/normasAssuntos
Antígeno Ki-1/análise , Micose Fungoide/diagnóstico , Síndrome de Sézary/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Bexaroteno/administração & dosagem , Humanos , Antígeno Ki-1/metabolismo , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/tratamento farmacológico , Micose Fungoide/patologia , Fotoferese , Síndrome de Sézary/sangue , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Linfócitos T/metabolismo , Resultado do Tratamento , Vorinostat/administração & dosagemRESUMO
Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by pruritic erythroderma, peripheral lymphadenopathy and the presence of malignant T cells in the blood. Unequivocal detection of malignant cells in patients with Sézary syndrome is of important diagnostic, prognostic and therapeutic value. However, no single Sézary syndrome specific cell surface marker has been identified. In a cohort of patients with Sézary syndrome, CD164 expression on total CD4+ lymphocytes was significantly upregulated compared with healthy controls. CD164 expression was in most cases limited to CD4+CD26- malignant T lymphocytes, unequivocally identified using flow-cytometry by the expression of a specific Vß clone for each patient. Increased expression of CD164 may be a promising diagnostic parameter and a potential target for a CD164-linked therapeutic approach in Sézary syndrome.
Assuntos
Biomarcadores Tumorais/sangue , Linfócitos T CD4-Positivos/imunologia , Síndrome de Sézary/sangue , Neoplasias Cutâneas/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Células Cultivadas , Dipeptidil Peptidase 4/sangue , Endolina/sangue , Feminino , Citometria de Fluxo , Humanos , Imunofenotipagem/métodos , Masculino , Pessoa de Meia-Idade , Fenótipo , Síndrome de Sézary/diagnóstico , Síndrome de Sézary/imunologia , Síndrome de Sézary/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/terapia , Resultado do TratamentoRESUMO
BACKGROUND: The rigorous cytological review by manual or automatic microscopic analysis is critical in the detection of circulating neoplastic cells, since their morphology as well as their count contributes to the diagnosis and prognosis of many diseases. However, the cytological analysis is not always obvious and requires trained and competent cytologist. In this context, the alarms and/or parameters generated by hematology analyzer could be particularly informative to alert the operators. METHODS: Blood samples from patients with Sezary syndrome (n = 9) were studied with Sysmex XN-1000 analyzer, and compared to patients with benign or tumoral skin lesions (n = 47) and patients with chronic lymphoproliferative B-cell diseases (n = 51) used as control. RESULTS: In present series, the value of structural lymphoid parameters (LyX and LyZ) and the alarm Blast/Abn Lympho were statistically higher in Sezary cases than in control cases. In addition, the value of LyX was associated to the count of circulating Sezary cells and value of LyZ to the presence of large Sezary cells, both parameters described as prognostic factors. CONCLUSION: The combination of alarm Blast/Abn Lympho and structural parameters (Ly-X/Ly-Z/Ly-Y) may allow to define rule of blood slide review to screen circulating Sezary cells, and give promising results in B-cell diseases.
Assuntos
Testes Hematológicos/instrumentação , Síndrome de Sézary/sangue , Linfócitos T/patologia , Autoanálise , Linfócitos B/patologia , Contagem de Células Sanguíneas , Núcleo Celular/patologia , Citoplasma/patologia , Diagnóstico Diferencial , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Extracorporeal photopheresis (ECP) is recommended for the erythrodermic mycosis fungoides (MF) and Sezary syndrome (SS) alone or in combination with other therapies. The possibility of a differential response in the blood and skin has hardly been addressed in the literature. OBJECTIVES: To evaluate the clinical response rate of patients with erythrodermic MF and SS to ECP as part of a multimodality approach and to compare the kinetics of the blood and skin responses in the presence of leukaemic involvement. METHODS: Twenty patients were treated with ECP and other modalities at a tertiary medical centre in 2003-2013. Ten patients had SS, 1 CD8-positive patch-stage MF with leukaemic involvement and nine erythrodermic MF. Clinical and outcome data were collected retrospectively from the medical files. Response was evaluated overall and for blood and skin separately. RESULTS: Adjunctive therapies were interferon-α, narrow-band ultraviolet B, psoralen and ultraviolet A, isotretinoin, acitretin, methotrexate, prednisone, topical nitrogen mustard and total skin or localized hands/feet electron beam radiotherapy. Overall response was documented in 13 patients (65%)--complete 30%, partial 35%--and maintained for >2 years in 38.5%. In patients with leukaemic involvement (n = 11), the blood response occurred earlier than skin response (P = 0.008) and was maintained longer (P = 0.03). In three of the patients with a complete blood response, the skin response was partial (n = 2) or absent (n = 1). CONCLUSION: Extracorporeal photopheresis as part of a multimodality approach yields a high durable clinical response in patients with erythrodremic MF and SS. The kinetics of the response differ between the blood and skin. The blood response occurs earlier and lasts longer; it does not necessarily predict the clinical skin response. Further studies are needed to determine if there is a survival advantage to a blood response in the absence of a skin response.
Assuntos
Micose Fungoide/terapia , Fotoferese , Síndrome de Sézary/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Dermatite Esfoliativa/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/complicações , Estudos Retrospectivos , Síndrome de Sézary/sangue , Síndrome de Sézary/complicações , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Immunological functions decline with age. Because MS/SzS predominately affects the elderly, it is important to distinguish age-related from cancer-specific changes. Also, MF and SzS are malignancies of CD4(+) T-lymphocytes, further compromising an immune state of the patients. The objectives of this study were to distinguish disease-specific immunological deterioration by performing comparative age-matched Luminex multiplex assessment of 34 serum biomarkers between patients with MF/SzS, HIV-infected individuals and normal controls. Controlling for age, expression level appears to significantly differ between patients with MF/SzS and controls for the following biomarkers: G-CSF, IL-5, MIP-1ß, TNF-α, VEGF, EOTAXIN, IL-8, IL-12, IL-2R, IP10, MCP-1, MIG, TNFR1 and TNFR2 (P < 0.05), while others showed normal age-related changes. Interestingly, cluster analysis placed MF/SzS profiles closer to HIV. This further underscores an immunologically compromised state of patients with MF/SzS and suggests its potential self-perpetuating role in disease progression.
Assuntos
Envelhecimento/sangue , Quimiocina CCL4/sangue , Fator Estimulador de Colônias de Granulócitos/sangue , Interleucina-5/sangue , Síndrome de Sézary/sangue , Neoplasias Cutâneas/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Progressão da Doença , Infecções por HIV/sangue , Humanos , Micose Fungoide/sangue , Síndrome de Sézary/diagnóstico , Neoplasias Cutâneas/diagnósticoRESUMO
Angioimmunoblastic T cell lymphoma (AITL) belongs to the subgroup of mature T cell lymphomas according to the World Health Organization and is one of the common T cell lymphomas in Western countries. Particularly in cases in which histological confirmation cannot be easily achieved, immunophenotyping of peripheral blood can give important information for the differential diagnosis of AITL. sCD3â» CD4⺠T cells are a typical feature of AILT in flow cytometry of peripheral blood. In this retrospective study, the diagnostic value of flow cytometry for the diagnosis 'AITL' was assessed by comparing the frequency of sCD3â» CD4⺠T cells in leukemic AITL patients and in patients with other leukemic CD4⺠T cell lymphomas. Immunophenotyping of peripheral blood by flow cytometry was performed in a lymphocyte gate using fluorochrome-labelled antibodies against CD3, CD2, CD4, CD5, CD7, CD8, CD10, CD14, CD16, CD19, CD56, CD57 and T cell receptor. In 17/17 leukemic AITL patients, a small but distinct population of sCD3â» CD4⺠T cells was detected (mean percentage of sCD3â» CD4⺠T cells in the lymphocyte gate: 11.9 ± 15.4%, range 0.1-51.8%). In contrast, sCD3â» CD4⺠T cells were found in only 1/40 patients with other leukemic CD4⺠T cell lymphomas (one patient with mycosis fungoides). sCD3â» CD4⺠T cells have a high positive predictive value (94%) for the diagnosis 'AITL'. Flow cytometry is particularly useful in the differential diagnosis of AITL, even if the aberrant T cell population has a very low frequency. Further biological characterization of this subfraction of lymphoma cells is warranted.
Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Complexo CD3/sangue , Antígenos CD4/sangue , Linfócitos T CD4-Positivos/patologia , Imunofenotipagem , Linfoma de Células T Periférico/sangue , Células-Tronco Neoplásicas/patologia , Subpopulações de Linfócitos T/patologia , Adulto , Idoso , Antígenos CD/sangue , Linfócitos T CD4-Positivos/química , Diagnóstico Diferencial , Feminino , Citometria de Fluxo , Humanos , Contagem de Linfócitos , Linfoma de Células T/sangue , Linfoma de Células T/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/química , Receptores de Antígenos de Linfócitos T/sangue , Síndrome de Sézary/sangue , Síndrome de Sézary/diagnóstico , Subpopulações de Linfócitos T/químicaAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Autoimunidade/efeitos dos fármacos , Síndrome de Sézary/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/farmacologia , Antineoplásicos/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Receptores CCR4/antagonistas & inibidores , Receptores CCR4/imunologia , Indução de Remissão/métodos , Síndrome de Sézary/sangue , Síndrome de Sézary/imunologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Angiogenesis is a crucial process in the growth and progression of cancer, correlating with the metastatic potential of tumour cells. Angiopoietins are ligands for the endothelium-specific tyrosine kinase Tie2 receptor, which comprise 4 structurally related proteins, termed angiopoietin (Ang)-1, Ang-2, Ang-3 and Ang-4. The roles of Ang-1 and Ang-2 have recently been clarified as crucial in angiogenesis. In this report, we measured serum Ang-1 and Ang-2 levels in patients with cutaneous T-cell lymphoma (CTCL). Serum levels of Ang-2, but not Ang-1, in patients with Sézary syndrome were significantly higher than those in patch mycosis fungoides (MF), plaque/tumour MF, and healthy controls. In patients with CTCL, serum Ang-2 correlated with disease activity. Moreover, the numbers of Ang-2+ cells in lesional skin of CTCL were significantly larger than those in normal skin. These results suggest that Ang-2 may have important roles in the development of CTCL.
Assuntos
Angiopoietina-1/sangue , Angiopoietina-2/sangue , Biomarcadores Tumorais/sangue , Micose Fungoide/sangue , Síndrome de Sézary/sangue , Neoplasias Cutâneas/sangue , Adulto , Idoso , Angiopoietina-1/análise , Angiopoietina-2/análise , Estudos de Casos e Controles , Quimiocinas CC/sangue , Progressão da Doença , Feminino , Humanos , Imunoglobulina E/sangue , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Micose Fungoide/química , Micose Fungoide/patologia , Neovascularização Patológica/sangue , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Receptores de Interleucina-2/sangue , Síndrome de Sézary/química , Síndrome de Sézary/patologia , Pele/irrigação sanguínea , Pele/química , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/química , Neoplasias Cutâneas/patologiaRESUMO
Many patients with cutaneous T-cell lymphoma (CTCL) experience severe pruritus. This study evaluated serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with CTCL. Although serum NGF and BDNF levels in patients with CTCL were not significantly higher than in healthy controls, serum NGF levels in patients with Sézary syndrome were higher than in those with mycosis fungoides and in healthy controls. Enhanced NGF expression by keratinocytes and increased dermal nerve fibres were detected in lesional skin of subjects with Sézary syndrome. Correlations between pruritus in CTCL and serum levels of NGF, BDNF, chemokine (C-C motif) ligand 1 (CCL1), CCL17, CCL26, CCL27, lactate dehydrogenase (LDH), IgE, and soluble interleukin-2 receptor were analysed. Serum CCL1, CCL26, LDH, and IgE levels correlated with pruritus in patients with CTCL. NGF may be associated with increased dermal nerve fibres and pruritus in Sézary syndrome, and CCL1, CCL26, and IgE may be associated with pruritus in CTCL.
Assuntos
Biomarcadores Tumorais/sangue , Quimiocina CCL1/sangue , Quimiocinas CC/sangue , Imunoglobulina E/sangue , Linfoma Cutâneo de Células T/imunologia , Fator de Crescimento Neural/sangue , Prurido/imunologia , Neoplasias Cutâneas/imunologia , Pele/inervação , Idoso , Fator Neurotrófico Derivado do Encéfalo/sangue , Estudos de Casos e Controles , Quimiocina CCL26 , Feminino , Humanos , Linfoma Cutâneo de Células T/sangue , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/sangue , Micose Fungoide/imunologia , Prurido/patologia , Síndrome de Sézary/sangue , Síndrome de Sézary/imunologia , Pele/patologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologiaRESUMO
MicroRNAs are commonly aberrantly expressed in many cancers. Very little is known of their role in T-cell lymphoma, however. We therefore elucidated the complete miRNome of purified T cells from 21 patients diagnosed with Sézary Syndrome (SzS), a rare aggressive primary cutaneous T-cell (CD4(+)) lymphoma. Unsupervised cluster analysis of microarray data revealed that the microRNA expression profile was distinct from CD4(+) T-cell controls and B-cell lymphomas. The majority (104 of 114) of SzS-associated microRNAs (P < .05) were down-regulated and their expression pattern was largely consistent with previously reported genomic copy number abnormalities and were found to be highly enriched (P < .001) for aberrantly expressed target genes. Levels of miR-223 distinguished SzS samples (n = 32) from healthy controls (n = 19) and patients with mycosis fungoides (n = 11) in more than 90% of samples. Furthermore, we demonstrate that the down-regulation of intronically encoded miR-342 plays a role in the pathogenesis of SzS by inhibiting apoptosis, and describe a novel mechanism of regulation for this microRNA via binding of miR-199a* to its host gene. We also provide the first in vivo evidence for down-regulation of the miR-17-92 cluster in malignancy and demonstrate that ectopic miR-17-5p expression increases apoptosis and decreases cell proliferation in SzS cells.
Assuntos
Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/fisiologia , Síndrome de Sézary/genética , Apoptose , Western Blotting , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Luciferases/metabolismo , Linfoma de Células B/sangue , Linfoma de Células B/diagnóstico , Linfoma de Células B/genética , MicroRNAs/genética , Micose Fungoide/sangue , Micose Fungoide/diagnóstico , Micose Fungoide/genética , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Sézary/sangue , Síndrome de Sézary/diagnóstico , Linfócitos T/metabolismoRESUMO
While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the N(ω)-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS.
Assuntos
Leucócitos Mononucleares/enzimologia , Macrófagos/enzimologia , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/sangue , Síndrome de Sézary/tratamento farmacológico , Síndrome de Sézary/enzimologia , Timopentina/farmacologia , Análise de Variância , Animais , Estudos de Casos e Controles , Bovinos , Regulação para Baixo/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Camundongos , Modelos Moleculares , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Proteínas Recombinantes/antagonistas & inibidores , Síndrome de Sézary/sangueRESUMO
Although Sézary syndrome (SS) represents an advanced stage of cutaneous T-cell lymphoma, this diagnosis presents a challenge even for the most experienced dermatologic clinicians. SS is characterized clinically by erythroderma, but can also be identified in the presence of specific histologic and peripheral blood findings. Erythrodermic cutaneous T-cell lymphoma can mimic a number of nonmalignant disorders with erythroderma, including pityriasis rubra pilaris, psoriasis, atopic dermatitis, and graft-versus-host disease. The diagnosis is made even more challenging because the histology of SS is often nonspecific and rarely pathognomonic. As a result, peripheral blood studies in patients with erythroderma are frequently informative in the diagnosis of SS. Peripheral blood abnormalities including elevated CD4/CD8 ratio, aberrant CD26, CD27 and CD7 expression, and T-cell clonality can all be used to help arrive at a diagnosis. This review evaluates current data on the usefulness and limitations of specific peripheral blood markers detected by flow cytometry and T-cell receptor gene rearrangement polymerase chain reaction.