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El virus linfotrópico de células T humanas tipo 1(HTLV-1, por sus siglas en inglés) es parte de la familia de los Retroviridae, perteneciente al género de los Delta retrovirus, está compuesto por una envoltura lipídica, obtenida de la célula huésped, en la superficie expresa proteínas transmembrana que le permite el anclaje e internalización por endocitosis al citoplasma celular. En su interior cuenta con una hebra de ARN de cadena simple en sentido positivo, además de las enzimas integrasa y transcriptasa inversa que forman la núcleo cápside icosaédrica. El virus linfotrópico de células T humanas está ampliamente distribuido a nivel mundial. Existen múltiples vías de transmisión (Transmisión vertical, interacciones sexuales, transfusiones sanguíneas, uso de drogas ilícitas endovenosas y el contacto de fluidos cargados de viriones con las mucosas). El 90% de los pacientes expuestos no desarrollaran síntomas, pero existe un 10% de los pacientes que desarrollaran el cuadro clínico. El HTLV-1 se asocia a dos cuadros clínicos bien establecidos: la paraparesia espática tropical y el linfoma cutáneo-T-leucemia de células T. Al ser inusual, presentándose en 1 de cada 100.000 habitantes, se discute el caso de una paciente femenina de 63 años de edad, con antecedentes de acalasia corregida quirúrgicamente, quien consulta con cuadro clínico de 2 meses de duración, caracterizado por debilidad progresiva simétrica en miembros inferiores que le impide la deambulación, incontinencia urinaria, lesiones cutáneas extensas y la presencia de hiperleucocitosis con más de 20% de blastos en sangre periférica, se realiza inmunofenotipo expresando que el 85% de linfocito T neoplásicos, resultando en leucemia de células T o síndrome de Sezary, posteriormente se confirma el diagnóstico al realizar Elisa de cuarta generación positivo para HTLV-1(AU)
The human T-cell lymphotropic virus is part of the Retroviridae family, belonging to the Delta retrovirus genus, thisvirus is composed of a lipid envelope, obtained from the hos tcell, on the surface it expresses transmembrane proteins that allow it to anchor and internalization by endocytosis into the cell cytoplasm. Inside it has a single-stranded RNA strand the positive direction, in addition to the enzymes integrase andreverse transcriptase that form the icosahedral nucleo capsid. Human T-cell T-cell lymphotrophic virus is widely distribute dworldwide. There are multiple routes of transmission (vertical transmission, sexual interactions, blood transfusions, use of intravenous illicit drugs and contact of virion-laden fluidswith mucous membranes). 90% of exposed patients will not develop symptoms, but there is 10% of patients who will develop the clinical picture, HTLV-1 is associated with twowell-established clinical pictures: tropical spastic paraplegia and cutaneous T-cell lymphoma. T-cell leukemia. As it is unusual, occurring in 1 out of every 100,000 inhabitants, the caseof a 63-year-old female patient with a history of surgically corrected achalasia is discussed, who consults with a clinical picture of 2 months duration, characterized due to progressive symmetrical weakness in the lower limbs that prevent walking, urinary incontinence, extensive skin lesions and the presence of hyperleukocytosis with more than 20% of blasts in peripheralblood, an immunophenotype is performed, expressing that 85% of neoplastic T lymphocytes, resulting in (T-cell leukemia) Sesary syndrome, diagnosis is later confirmed by performing afourth generation Elisa positive for HT LV-1(AU)
Subject(s)
Humans , Female , Middle Aged , RetroviridaeABSTRACT
Introducción: El virus linfotrópico de células T humanas tipo 1 es el retrovirus causal de la leucemia-linfoma de células T. Su escaso diagnóstico en fases agudas hace que encontrar un biomarcador acertado para conocer el desarrollo de la leucemia sea de interés clínico y científico. Objetivo: Presentar la proteína basic zipper protein como marcador diagnóstico y de seguimiento al tratamiento de la leucemia-linfoma de células T. Métodos: Se consultó material académico en diferentes bases de datos científicas tales como PubMed, Springerlink, Proquest y Sciencedirect. Se tuvieron en cuenta criterios como datos, efectividad en la identificación y amplificación de basic zipper protein, reconocimiento de las fases del virus linfotrópico de células T, epidemiología y mecanismos moleculares en la patogenia del virus. Análisis y síntesis de la información: La basic zipper protein es una proteína del virus linfotrópico de células T indispensable para el proceso de leucemogénesis, capaz de interactuar con factores endógenos del huésped, lo que la convierte en marcador de la enfermedad. Conclusiones: La basic zipper protein cuenta con características que la perfilan para ser el biomarcador con mayor predicción de la enfermedad por su estabilidad e importancia en la leucemogénesis. Además, el nivel de ARNm de la basic zipper protein es mayor en leucemia-linfoma de células T.
Introduction: Human T-cell lymphotropic virus type 1 is the retrovirus that causes T-cell leukemia-lymphoma. Its scarce diagnosis in acute phases means that finding an accurate biomarker to determine the development of leukemia is of clinical and scientific interest. Objective: To present the basic zipper protein as a diagnostic and follow-up marker for treatment of T-cell leukemia-lymphoma. Methods: Academic material was consulted in different scientific databases such as PubMed, Springerlink, Proquest and Sciencedirect. Criteria such as: data, effectiveness in the identification and amplification of basic zipper protein, recognition of the phases of the T-cell lymphotropic virus, epidemiology and molecular mechanisms in the pathogenesis of the virus were taken into account. Analysis and synthesis of the information: The basic zipper protein is a protein of the T-cell lymphotropic virus essential for the leukemogenesis process, capable of interacting with endogenous factors of the host, which makes it a marker of the disease. Conclusions: The Basic zipper protein has characteristics that outline it to be the biomarker with the highest prediction of the disease due to its stability and importance in leukemogenesis. In addition, the mRNA level of the basic zipper protein is higher in T-cell leukemia-lymphoma.
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HumansABSTRACT
Objective:To analyze the expression of human leukocyte antigen G (HLA-G) in human T-cell leukemia virus type 1 (HTLV-1)-positive T cells, and to investigate its role in the occurrence and development of HTLV-1 infection.Methods:The expression of HLA-G in HTLV-1-positive T cell lines (MT2 and MT4) was detected by Western blot and real-time PCR. HLA-G gene in MT2 and MT4 cells was knocked down by siRNA, and the effects of HLA-G on the expression of HTLV-1 Tax and P19 at mRNA and protein levels were detected by Western blot and real-time PCR. Moreover, the changes in cytokine expression in MT2 and MT4 cells were monitored at RNA level after HLA-G gene silencing. The proliferation ability of MT2 and MT4 cells was analyzed by CCK8. Signal transducer and activator of transcription 3 (STAT3) pathway-related proteins were detected by Western blot.Results:Compared with HTLV-1-negative T cells (Jurkat and MOLT4), the expression of HLA-G increased significantly in MT2 and MT4 cells. After knocking down the HLA-G gene with siRNA in MT2 and MT4 cells, the expression of HTLV-1 Tax and P19 at mRNA and protein levels was decreased, and the expression of antiviral cytokines IFN-γ and TNF-α was increased. The proliferation of MT2 and MT4 cells and STAT3 phosphorylation in these cells were decreased.Conclusions:HTLV-1 could induce T cells to overexpress the immune tolerance molecule HLA-G. Silencing HLA-G gene in HTLV-1-positive T cells could promote the production of antiviral cytokines and reduce IL-6 expression and STAT3 phosphorylation, thereby effectively inhibiting the replication of HTLV-1.
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Resumen La leucemia de células T grandes granulares es un trastorno poco frecuente de linfocitos citotóxicos. Estas células juegan un rol integral en el sistema inmunológico y se dividen en 2 linajes: T CD3 positivas y natural killer. Su proliferación y citotoxicidad descontrolada puede generar autoinmunidad o malignidad. La artritis reumatoide es la enfermedad autoinmune más común en individuos con este tipo de leucemia, sin embargo, se ha asociado a un amplio espectro de otras enfermedades autoinmunes y afecciones hematológicas incluyendo anemia hemolítica, aplasia pura de glóbulos rojos y neutropenia, que conducen a infecciones bacterianas recurrentes. Se presenta a continuación una paciente de 72 años con antecedentes de leucemia de células T grandes granulares y manifestaciones compatibles con artritis reumatoidea, que intercurre con un Síndrome de Evans grave con buena respuesta inicial y sostenida a gammaglobulina, corticoterapia, y rituximab.
Abstract Large granular T-cell leukemia is a rare cytotoxic lymphocyte disorder. These cells play an integral role in the immune system and are divided into 2 lineages: CD3 T positive and natural killer. Its proliferation and uncontrolled cytotoxicity can generate autoimmunity or malignancy. Rheumatoid arthritis is the most common autoimmune disease in individuals with this type of leukemia, however, it has been associated with a wide spectrum of other autoimmune diseases and hematological conditions including hemolytic anemia, pure red blood cell aplasia, and neutropenia, leading to recurring bacterial infections. The following is a case of a 72-year-old female with a history of large granular T-cell leukemia and manifestations compatible with rheuma toid arthritis, which occurs with a severe Evans syndrome with a good initial and sustained response to gamma globulin, corticosteroid therapy, and rituximab.
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Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.
Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.
Subject(s)
Humans , Male , Adult , Middle Aged , Human T-lymphotropic virus 1/genetics , HTLV-I Infections/diagnosis , Leukemia-Lymphoma, Adult T-Cell/diagnosis , T-LymphocytesABSTRACT
Objective To investigate whether cyclic GMP-AMP synthase ( cGAS ) , a cytosolic DNA sensor, could recognize the reverse transcription intermediate and induce the subsequent signaling path-way during the infection of human T cell leukemia virus type 1 ( HTLV-1 ) . Methods Biotin-labeled ssDNA90, a reverse transcription intermediate of HTLV-1, was transfected into HeLa cells and the interac-tion between it and cGAS was detected by co-immunoprecipitation experiments. HeLa cells were co-cultured with HTLV-1-positive MT2 cells and the interaction between cGAS and stimulator of interferon genes ( STING) was analyzed by co-immunoprecipitation experiments. The expression of STING in HeLa cells was silenced by siRNA. cGAS was transfected into the HeLa cells 24 h after the silencing and after 24 h, these cells were co-cultured with MT2 cells for another 24 h. Real-time PCR assay was used to measure the ex-pression of IFN-β, RANTES ( regulated upon activation, normal T-cell expressed, and secreted) , TNF-α, HTLV-1 protein Tax, p19 and HBZ. Immunoblot assay was performed to evaluate the phosphorylation of IRF3 and p65 in HeLa cells. Results cGAS interacted with ssDNA90. cGAS interacted with STING in the cytoplasm. In STING-silenced HeLa cells, cGAS transfection had no influence on the expression of IFN-β, RANTES , TNF-α, Tax , p19 or HBZ , nor did it affect the phosphorylation of IRF3 or p65 . Conclusions cGAS interacted with HTLV-1 RTI ssDNA90 and activated STING-dependent innate immune responses.
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Objective@#To investigate the effects of interferon inducible protein 16 (IFI16), a cytosolic DNA sensor, on the expression of human T-cell leukemia virus type 1 (HTLV-1) proteins and pro-inflammatory cytokines in adult HTLV-1-positive T cells.@*Methods@#IFI16 expression in different HTLV-1-positive T cell lines was detected by immunoblot assay. Specific siRNA targeting the IFI16 gene was constructed and the gene silencing efficiency was detected by immunoblot assay. Expression of HTLV-1 Tax protein at mRNA and protein levels was respectively detected by real-time PCR and immunoblot assay after knocking down the expression of IFI16 in HTLV-1-positive T cells with siRNA. Expression of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, Tax and Env were detected by real-time PCR.@*Results@#Compared with the HTLV-1-negative T cell line Jurkat, IFI16 expression was enhanced in the HTLV-1-positive T cell lines MT2, MT4 and C8166. Tax expression was increased, while that of IFN-α, IFN-γ and TNF-α was decreased in MT2 and MT4 cells after silencing the expression of IFI16 with siRNA.@*Conclusions@#IFI16 expression was increased in HTLV-1-positive MT2 and MT4 cells. Meanwhile, IFI16 promoted the production of interferon and pro-inflammatory cytokines and inhibited the expression of HTLV-1 proteins.
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Objective To investigate the effects of interferon inducible protein 16 (IFI16), a cy-tosolic DNA sensor, on the expression of human T-cell leukemia virus type 1 (HTLV-1) proteins and pro-in-flammatory cytokines in adult HTLV-1-positive T cells. Methods IFI16 expression in different HTLV-1-positive T cell lines was detected by immunoblot assay. Specific siRNA targeting the IFI16 gene was con-structed and the gene silencing efficiency was detected by immunoblot assay. Expression of HTLV-1 Tax pro-tein at mRNA and protein levels was respectively detected by real-time PCR and immunoblot assay after knocking down the expression of IFI16 in HTLV-1-positive T cells with siRNA. Expression of interferon ( IFN)-α, IFN-γ, tumor necrosis factor ( TNF )-α, Tax and Env were detected by real-time PCR. Re-sults Compared with the HTLV-1-negative T cell line Jurkat, IFI16 expression was enhanced in the HTLV-1-positive T cell lines MT2, MT4 and C8166. Tax expression was increased, while that of IFN-α, IFN-γand TNF-α was decreased in MT2 and MT4 cells after silencing the expression of IFI16 with siRNA. Con-clusions IFI16 expression was increased in HTLV-1-positive MT2 and MT4 cells. Meanwhile, IFI16 pro-moted the production of interferon and pro-inflammatory cytokines and inhibited the expression of HTLV-1 proteins.
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CD4 counts along with viral loads are important parameters in the monitoring of human immunodeficiency virus (HIV) infection. Human T-cell lymphotropic virus type I (HTLV-I) is known to be an etiological agent for adult T-cell leukemia/lymphoma (ATLL). Coinfection of HTLV-I and HIV is well known in regions with high seroprevalence, and there is no published data in the Indian scenario. We present an interesting case of occurrence of CD4+ T-cell proliferation in a known beta thalassemia major with acquired HIV seropositivity accompanied by simultaneously increasing CD4+ counts and viral loads. Further workup revealed ATLL with an underlying HTLV infection.
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We studied the effect of celastrol on the proliferation and apoptosis of adult T-cell leukemia (ATL) cells. After treating adult T-cell leukemia cell lines with different concentrations of celastrol, we analyzed the cell proliferation by MTT and colony formation assays. Flow cytometry was conducted to detect cell apoptosis by Annexin V-FITC/PI staining. Western blotting and dual-luciferase reporter assay were done to study the mechanism how celastrol suppressed the growth of adult T-cell leukemia cells. Celastrol could significantly inhibit the proliferation of adult T-cell leukemia cells, and induce apoptosis of ATL cells. With the increase of the concentration of celastrol, the ratio of Bax/Bcl-2 protein was up-regulated. The Caspase-3/7 protein was cleaved and activated after treatment with celastrol. Moreover, the expression of HTLV-1-encoded viral protein Tax was significantly inhibited in the celastrol treated cells. Taken together, these results indicated that celastrol effectively inhibited the proliferation of adult T-cell leukemia cells by regulating the expression of Bcl-2 family protein, and induced cell apoptosis by activating Caspase dependent pathway. In addition, celastrol could inhibit the expression of viral protein Tax. This study will provide an experimental basis for the clinical application of celastrol in the treatment of adult T-cell leukemia.
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Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Human T-lymphotropic virus 1 , HTLV-I Infections , Leukemia-Lymphoma, Adult T-Cell , Zidovudine , Leukemia , Lymphoma, T-Cell, PeripheralABSTRACT
Abstract Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.
Subject(s)
Humans , Female , Middle Aged , Hodgkin Disease/pathology , HTLV-I Infections/pathology , Leukemia-Lymphoma, Adult T-Cell/pathology , Lymphocytosis/pathology , Biopsy , Enzyme-Linked Immunosorbent Assay , Hodgkin Disease/virology , Human T-lymphotropic virus 1/isolation & purification , Leukemia-Lymphoma, Adult T-Cell/virology , Fatal Outcome , Lymphocytosis/virology , Lymph Nodes/pathologyABSTRACT
Objective To investigate the influence of early growth response gene-1 (EGR1) on the autophagy of host cells following infection with human T cell leukemia virus type 1 (HTLV-1).MethodsA HTLV-1-positive cell line MT2 was co-cultured with HeLa cells for 24 h to construct the virus early infection model.Immunoblotting assay was used to detect the expression of HTLV-1 core protein p19 and EGR1.Luciferase reporter gene analysis was used to detect the transcriptional activity of 5′-regulatory sequence of EGR1 at different time points after co-culturing.An effective small interfering RNA (siRNA) targeting EGR1 was screened out and transfected into HeLa cells by Lipofectamine 2000.Then the transfected HeLa cells were co-cultured with the HTLV-1-positive cell line MT2 for 24 h.Immunoblotting assay was used to detect HTLV-1 core protein p19, EGR1 and autophagy-related protein LC3.Real-time PCR was performed to detect viral load.Autophagosome was analyzed by immunofluorescence after co-culturing.Results The expression of EGR1 and the transcriptional activity of pEGR1-luc gradually increased after co-culturing HeLa cells with MT2 cells for 8 h (P<0.01).The expression of EGR1 was positively correlated with host cell autophagy following HTLV-1 infection.The effective siRNA for silencing the expression of EGR1 was obtained and named as siE2.The viral load, the expression of HTLV-1 core protein p19 and the proportion of LC3B/LC3A in the co-culture model were markedly down-regulated by RNA interference with siE2, which was concomitant with a persistent decrease of intracellular autophagosome (P<0.01).Conclusion EGR1 is associated with host cell autophagy and viral replication in HTLV-1 infection.
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Objective To investigate the function and the possible mechanism of cyclic GMP-AMP synthase (cGAS), a DNA sensor, in HeLa cells during human T cell leukemia virus type 1 (HTLV-1) in-fection.Methods HeLa cells were co-cultured with MT2 cells (HTLV-1-positive T cells) and then detec-ted by immunoblot assay to analyze the changes in the expression of cGAS .A hemagglutinin ( HA)-tagged cGAS plasmid was constructed and transfected into HeLa cells .Twenty-four hours after transfection , these cells were co-cultured with MT2 cells for another 24 hours.Immunoblot assay was used to detect the expres-sion of HTLV-1 proteins Tax and p19.Real-time PCR was performed to measure the expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level .Immunoblot assay was also used to analyze the phosphorylation of interferon regulatory factor 3 (IRF3) and p65.Expression of interferon (IFN)-β, IFN-gamma-inducible protein 10 ( IP-10 ) , RANTES ( regulated on activation , normal T cell expressed and secreted ) and tumor necrosis factor (TNF)-αwas detected by real-time PCR assay.Results Expression of cGAS was enhanced in HeLa cells after co-cultured with MT2 cells.Compared with control cells , the HeLa cells that were trans-fected with cGAS plasmid showed lower levels of Tax and p 19 proteins, suppressed expression of HTLV-1 Tax, p19, Env, HBZ and px at mRNA level , enhanced phosphorylation of IRF 3 and p65, and higher levels of IFN-β, IP-10, RANTES and TNF-αafter co-cultured with MT2 cells.Conclusion cGAS might promote the innate immune response and inhibit HTLV-1 replication in HTLV-1-infected HeLa cells .
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Summary Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Twenty million people are believed to be infected throughout the world, mostly in Japan, Africa, the Caribbean, and South America, particularly in Brazil and Peru. ATL affects about 5% of infected individuals and is classified in the following clinical forms: acute, lymphoma, primary cutaneous tumoral, chronic (favorable and unfavorable), and smoldering (leukemic and non-leukemic). Although it is considered an aggressive disease, there are cases with a long progression. We emphasize the importance of clinical classification as an indispensable element for evaluating prognosis and appropriate therapeutic approach. Since several cases have been published in Brazil and this disease is still poorly known, we decided to make a review paper for dissemination of clinical, hematological and pathological aspects, diagnosis, and therapy. The best way to reduce the occurrence of ATL would be halting the transmission of the virus through breastfeeding.
Resumo A leucemia/linfoma de células T do adulto (LLcTA) é uma neoplasia de células T maduras CD4+ causada pelo vírus linfotrópico para células T humanas tipo 1 (HTLV-1). Acredita-se que existem cerca de 20 milhões de pessoas infectadas em todo o mundo, principalmente no Japão, na África, no Caribe e na América do Sul, particularmen te no Brasil e no Peru. A LLcTA acomete cerca de 5% dos indivíduos infectados e classifica-se nas seguintes formas clínicas: aguda, linfomatosa, tumoral primária de pele, crônica (favorável e desfavorável) e indolente (leucêmica e não leucêmica). Embora seja considerada uma doença agressiva, há casos com longa evolução. Salientamos a importância da classificação clínica como elemento im prescindível para avaliação do prognóstico e conduta terapêutica adequada. Como já foram publicados vários casos no Brasil e essa doença ainda é pouco conhecida, decidimos fazer um trabalho de revisão para divulgar os seus aspectos clínicos, hematológicos, anatomopatológi cos, diagnósticos e terapêuticos. O melhor meio de redu zir a ocorrência de LLcTA seria sustando a transmissão vertical do vírus pela amamentação.
Subject(s)
Humans , Adult , Leukemia-Lymphoma, Adult T-Cell/pathology , Skin/pathology , Biopsy , Human T-lymphotropic virus 1 , Leukemia-Lymphoma, Adult T-Cell/classification , Leukemia-Lymphoma, Adult T-Cell/therapy , Chronic DiseaseABSTRACT
Publications are often used as a measure of research work success. Human T-lymphotropic virus (HTLV) type 1 and 2 are human retroviruses, which were discovered in the early 1980s, and it is estimated that 15-20 million people are infected worldwide. This article describes a bibliometric review and a coauthorship network analysis of literature on HTLV indexed in PubMed in a 24-year period. A total of 7,564 documents were retrieved, showing a decrease in the number of documents from 1996 to 2007. HTLV manuscripts were published in 1,074 journals. Japan and USA were the countries with the highest contribution in this field (61%) followed by France (8%). Production ranking changed when the number of publications was normalized by population (Dominican Republic and Japan), by gross domestic product (Guinea-Bissau and Gambia), and by gross national income per capita (Brazil and Japan). The present study has shed light on some of the defining features of scientific collaboration performed by HTLV research community, such as the existence of core researchers responsible for articulating the development of research in the area, facilitating wider collaborative relationships and the integration of new authors in the research groups.
Subject(s)
Humans , Bibliometrics , Biomedical Research/statistics & numerical data , Human T-lymphotropic virus 1 , Cooperative Behavior , Geography , Global Health , HTLV-I Infections/virology , Periodicals as Topic/statistics & numerical dataABSTRACT
Objective:To investigate the effect on proliferation and apoptosis of T-cell leukemia cells by silencing NRP-1 ( Jurkat cells).Methods:The lentivirus plasmid which expresses NRP1 gene specific shRNA was constructed in our preliminary ex-perimental.We transfected the lentivirus plasmid to human T-cell Lymphoma cells.The proliferation of Jurkat cells different groups and effect on cell proliferation after chemotherapy drug EPI-treated were found by CCK-8 kit.The proliferation level and apoptosis rate of the cells were detected by flow cytometry and Annexin-V-FITC/PI method.Results:The proliferation level of NRP-1 /shRNA interference group was decreased significantly in 48 h,72 h,96 h,which was compared with the control groups.The apoptosis rate of the NRP-1/shRNA interference group was increased compared with control groups.The chemotherapy drug sensitivity of epirubicin ( EPI ) test results showed that EPI concentration was 0.025,0.05,0.1,0.2,0.4 μg/ml,the NRP-1/shRNA interference group of cell growth inhibition rate was increased,the corresponding control group difference had statistical significance(P<0.05).We choose the drug con-centration of the EPI IC50 for next experiments.NRP-1/shRNA interference group cell apoptosis rate increased significantly after induction,compared with the control groups difference was statistically significant ( P<0.05 ).Compared with control group, the expression level of Bcl-2 protein was decreased and the expression level of bax protein was increased significantly after EPI induction.The percentage of cells at G0/G1 phase increased significantly,while those at S phase decreased significantly.Conclusion:Plasmid shRNA-NRP1 inhibited the expression of NRP1 in Jurkat cells and decreased the proliferation level of Jurkat cells and promote their apoptosis and enhance their drug sensitivity;the molecular mechanism may relate to down-regulation of Bcl-2 and up-regulation of Bax.and arrested the cell cycle at G0/G1 phase.
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Objective To explore the expression of early growth response gene-1 (EGR-1) in T cells that were positive for Tax protein of human T-cell leukemia virus type 1 (HTLV-1) and its possible reg-ulatory mechanism .Methods A series of expression structures carrying the regulatory elements of EGR-1 in different length and luciferase reporter genes were constructed .TaxP cells were transfected with the con-structs containing reporter genes and cultured with 5μmol/L of NF-κB inhibitor BAY 11-7082 or equal vol-ume of DMSO.After cultured for 24 hours the cells were collected to test the luciferase activity .BAY 11-7082 or equal volume of DMSO was added into the supernatant of TaxP cell culture to test the expression of EGR-1 protein by Western blot after 24 hours of culture .Tax and its mutants M22 and M47 were transfected into 293 T cells respectively to test the expression of EGR-1 protein by Western blot after 24 hours of culture . Results The expression structures carrying the regulatory elements of EGR-1 in different length and their mutants followed by luciferase reporter genes were successfully constructed .The luciferase activity in the cells transfected with the constructs containing the elements E 1 and E2 were higher than that transfected with E3, DelE and MutE, but the reporter gene expressions were decreased with the interference of BAY 11-7082 (P<0.01).However, there were no significant changes with the luciferase activity in the cells transfected by elements E3, DelE and MutE.Western blot analysis indicated that the expression of EGR-1 protein was significantly decreased with the interference of BAY 10-7082 .The expression of EGR-1 protein in M22 mu-tants-transfected 293 T cells were decreased significantly in comparison with those by wild type tax-and M47-transfected cells .Conclusion NF-κB was the key nuclear factor in regulating the expression of EGR-1 pro-tein in Tax-positive T cells .
ABSTRACT
Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that is geographically clustered, mirroring areas endemic for human T-cell lymphotropic virus type 1 infection. Most patients with ATLL present with aggressive manifestations such as severe hypercalcemia, lymphadenopathy, hepatosplenomegaly, and bone marrow involvement with progressive thrombocytopenia. We herein report a case of a patient with ATLL exhibiting increased uptake in both lungs as shown on a bone scan using 99mTc-methylene diphosphonate. This finding is thought to have been caused by metastatic calcification associated with ectopic parathyroid hormone production.
Subject(s)
Adult , Humans , Bone Marrow , Calcinosis , Hypercalcemia , Leukemia-Lymphoma, Adult T-Cell , Lung , Lymphatic Diseases , Parathyroid Hormone , T-Lymphocytes , Technetium Tc 99m Medronate , ThrombocytopeniaABSTRACT
The adult T-cell leukemia/lymphoma (ATLL) is a rare type of lymphoma caused by human T lymphotropic virus type 1 (HTLV-1). The clinical manifestations include cutaneous lesions, adenopathies, myelopathy/ tropical spastic paraparesis, uveitis, ophthalmological diseases, leukocytosis with lymphocytosis and atypical lymphocytes. The main objective of this study was to report a case of a female patient with ATLL, a farmer with leukocytosis, lymphocytosis, bilateral ocular erythema, cervical lymphadenopathy, in the abdominal visceromegalies and with positive markers for T-cell lymphocytes (CD45, CD2, CD3, CD5, CD4 and CD25). Although ATLL is a rare disease, its delayed diagnosis may lead to serious complications and fatal outcome.
O linfoma/leucemia de células T do adulto (ATLL) é um tipo raro de linfoma causado pelo vírus T-linfotrópico humano tipo I (HTLV-1). O quadro clínico inclui lesões de pele, adenomegalias, mielopatia/paraparesia espástica tropical, uveíte, doença oftalmológica, leucocitose com linfocitose e linfócitos atípicos. O objetivo deste estudo foi relatar o caso de uma paciente com ATLL, agricultora, com leucocitose, linfocitose, eritema ocular bilateral, linfadenopatia cervical, sem visceromegalias abdominais e com marcadores positivos para linfócitos T (CD45, CD2, CD3, CD5, CD4 e CD25). Embora a ATLL seja uma doença rara, a demora no seu diagnóstico pode levar a sérias complicações e ocasionar a morte do paciente.