RESUMEN
Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients' samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-ß, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs' roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.
Asunto(s)
Infecciones por HTLV-I , Leucemia-Linfoma de Células T del Adulto , MicroARNs , Biología Computacional , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/virología , MicroARNs/genéticaRESUMEN
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy of CD4+ T-cells associated with HTLV-1 infection. In this study, we used the model of immunodeficient NSG mice reconstituted with a functional human immune system (HIS) to investigate early events in HTLV-1 pathogenesis. Upon infection, human T-cells rapidly increased in the blood and lymphoid tissues, particularly CD4+CD25+ T-cells. Proliferation of CD4+ T-cells in the spleen and mesenteric lymph nodes (MLN) correlated with HTLV-1 proviral load and CD25 expression. In addition, splenomegaly, a common feature of ATLL in humans, was also observed. CD4+ and CD8+ T-cells predominantly displayed an effector memory phenotype (CD45RA-CCR7-) and expressed CXCR3 and CCR5 chemokine receptors, suggesting the polarization into a Th1 phenotype. Activated CD8+ T-cells expressed granzyme B and perforin; however, the interferon-γ response by these cells was limited, possibly due to elevated PD-1 expression and increased frequency of CD4+FoxP3+ regulatory T-cells in MLN. Thus, HTLV-1-infected HIS-NSG mice reproduced several characteristics of infection in humans, and it may be helpful to investigate ATLL-related events and to perform preclinical studies. Moreover, aspects of chronic infection were already present at early stages in this experimental model. Collectively, we suggest that HTLV-1 infection modulates host immune responses to favor viral persistence.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Diferenciación Celular/inmunología , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Leucemia-Linfoma de Células T del Adulto/inmunología , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Antígenos Comunes de Leucocito/metabolismo , Ratones , Infección Persistente/inmunología , Infección Persistente/virologíaRESUMEN
BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2-5% of the infected individuals. Host genetic background might play a role in disease progression. Several previous studies across many countries report HLA haplotype to be one such factor. Here, we sequenced HLA-A, -B and -C of 66 individuals by Sequence-Based Typing (SBT), and compared the frequency of different alleles among ATLL patients, HAM/TSP patients, asymptomatic carriers and non-infected individuals living in Argentina. RESULTS: The frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02, HLA-B*35 and HLA-C*07 as associated to protection from ATLL (p = 0.031), susceptibility to HAM/TSP (p < 0.001) and susceptibility to ATLL (p = 0.017), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p = 0.008), but were unable to identify any particular allele associated with high or low PVL. CONCLUSIONS: We have found HLA-A*02, HLA-B*35 and HLA-C*07 to be associated to protection from ATLL (HLA-A*02) and susceptibility to HAM/TSP (HLA-B*35) or to ATLL (HLA-C*07), respectively. Whereas HLA-A*02 protection from ATLL has already been extensively described in other regions of the world, this is the first report that links HLA-B*35 and an increased susceptibility to HAM/TSP. As for HLA-C*07 it has previously been associated to susceptibility to HAM/TSP in other countries but in our population it has been linked to ATLL.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Antígeno HLA-B35/genética , Infecciones por HTLV-I/genética , Paraparesia Espástica Tropical/genética , Adolescente , Adulto , Alelos , Argentina , Progresión de la Enfermedad , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Antígeno HLA-A2/genética , Antígenos HLA-C/genética , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/genética , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Persona de Mediana Edad , Paraparesia Espástica Tropical/virología , Provirus/genética , Carga Viral , Adulto JovenRESUMEN
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the human T-cell leukemia virus type 1 (HTLV-1). It is characterized by a short survival time and lack of response to chemotherapy. We report a case of a 56-year-old woman, from the Brazilian northeast state of Bahia, who presented with a 2-month history of infiltrated papular and nodular skin lesions, especially on her forehead and also on her lower and upper limbs. Laboratory tests revealed positive serology for HTLV-1. Histopathological findings and the immunohistochemical profile confirmed the diagnosis of adult T-cell lymphoma/leukemia. A month after the diagnosis, the patient presented acute fatigue and pronounced paleness of the skin, dying of septic shock after her first chemotherapy cycle. The aim of this case report was to emphasize the importance of maintaining high clinical suspicion for ATLL, considering the epidemiological profile of the disease, especially for patients whose only early symptoms are cutaneous lesions.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Piel/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Resultado Fatal , Femenino , Infecciones por HTLV-I/patología , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Persona de Mediana Edad , Prednisona/uso terapéutico , Vincristina/uso terapéuticoRESUMEN
Adult T-cell lymphoma is an aggressive and poor prognosis HTLV1-associated lymphoma. There is no standard treatment, but it is known that intensive chemotherapy regimens are necessary, with or without concomitant antiretroviral therapy, plus consolidation with allogeneic stem cell transplantation. Our case report shows a favorable outcome after 2 cycles of chemotherapy and allogeneic stem cell transplantation without antiretroviral agents, achieving complete remission, and a negative proviral load.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia-Linfoma de Células T del Adulto/terapia , Adulto , Antirretrovirales/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Etopósido/uso terapéutico , Virus Linfotrópico T Tipo 1 Humano , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Prednisolona/uso terapéutico , Provirus , Inducción de Remisión , Trasplante Homólogo , Resultado del Tratamiento , Vincristina/uso terapéutico , Carga ViralRESUMEN
Synthesis of four compounds belonging to mesoionic class, (E)-3-phenyl-5-(phenylamino)-2-styryl-1,3,4-thiadiazol-3-ium chloride derivatives (5a-d) and their biological evaluation against MT2 and C92 cell lines infected with human T-cell lymphotropic virus type-1 (HTLV-1), which causes adult T-cell leukemia/lymphoma (ATLL), and non-infected cell lines (Jurkat) are reported. The compounds were obtained by convergent synthesis under microwave irradiation and the cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Results showed IC50 values of all compounds in the range of 1.51-7.70 M in HTLV-1-infected and non-infected cells. Furthermore, it was observed that 5b could induce necrosis after 24 h for Jurkat and MT2 cell lines. The experimental (fluorimetric method) and theoretical (molecular docking) results suggested that the mechanism of action for 5b could be related to its capacity to intercalate into DNA. Moreover, the preliminary pharmacokinetic profile of the studied compounds (5a-d) was obtained through human serum albumin (HSA) binding affinity using multiple spectroscopic techniques (circular dichroism, steady-state and time-resolved fluorescence), zeta potential and molecular docking calculations. The interaction HSA:5a-d is spontaneous and moderate (Ka ~ 104 M-1) via a ground-state association, without significantly perturbing both the secondary and surface structures of the albumin in the subdomain IIA (site I), indicating feasible biodistribution in the human bloodstream.
Asunto(s)
Antineoplásicos/farmacología , Cloruros/farmacología , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/virología , Sitios de Unión , Línea Celular Tumoral , Supervivencia Celular , Dicroismo Circular , Ensayos de Selección de Medicamentos Antitumorales , Virus Linfotrópico T Tipo 1 Humano , Humanos , Concentración 50 Inhibidora , Células Jurkat , Espectroscopía de Resonancia Magnética , Microondas , Simulación del Acoplamiento Molecular , Unión Proteica , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica Humana/química , Distribución TisularRESUMEN
The HTLV-1 is the first human retrovirus and is associated with several clinical syndromes, however, the pathogenesis of these clinical manifestations is still not fully understood. Furthermore, there are few complete genomes publicly available, about 0.12 complete genomes per 10,000 infected individuals and the databases have a major deficiency of sequences information. This study generated and characterized 31 HTLV-1 complete genomes sequences derived from individuals with Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (TSP/HAM), Adult T-cell leukemia/lymphoma (ATL), infective dermatitis associated to HTLV-1 (IDH) and asymptomatic patients. These sequences are associated to clinical and epidemiological information about the patients. The sequencing data generated on Ion Torrent PGM platform were assembled and mapped against the reference HTLV-1 genome. These sequences were genotyped as Cosmopolitan subtype, Transcontinental subgroup. We identified the variants in the coding regions of the genome of the different clinical profiles, however, no statistical relation was detected. This study contributed to increase of HTLV-1 complete genomes in the world. Furthermore, to better investigate the contribution of HTLV-1 mutations for the disease outcome it is necessary to evaluate the interaction of the viral genome and characteristics of the human host.
Asunto(s)
Dermatitis/virología , Virus Linfotrópico T Tipo 1 Humano/clasificación , Leucemia-Linfoma de Células T del Adulto/virología , Paraparesia Espástica Tropical/virología , Secuenciación Completa del Genoma/métodos , Adolescente , Adulto , Anciano , Niño , Femenino , Variación Genética , Tamaño del Genoma , Genoma Viral , Secuenciación de Nucleótidos de Alto Rendimiento , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Adulto JovenRESUMEN
Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.
Asunto(s)
Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/virología , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Ensayo de Inmunoadsorción Enzimática , Resultado Fatal , Femenino , Humanos , Linfadenopatía/virología , Adulto JovenRESUMEN
The human T cell lymphotropic virus type 1 (HTLV-1) infects 5 to 10 million individuals and remains without specific treatment. This retrovirus genome is composed of the genes gag, pol, env, and a region known as pX. This region contains four open reading frames (ORFs) that encode specific proteins. The ORF-I produces the protein p12 and its cleavage product, p8. In this study, we analyzed the genetic diversity of 32 ORF-I sequences from patients with different clinical profiles. Seven amino acid changes with frequency over 5% were identified: G29S, P34L, L55F, F61L, S63P, F78L, and S91P. The identification of regions where the posttranslational sites were identified showed a high identity among the sequences and the amino acid changes exclusive of specific clinical profile were found in less than 5% of the samples. We compare the findings with 2.406 sequences available in GenBank. The low overall genetic diversity found suggested that this region could be used in the HTLV-1 vaccine development.
Asunto(s)
Variación Genética , Infecciones por HTLV-I/virología , Virus Linfotrópico T Tipo 1 Humano/genética , Sistemas de Lectura Abierta , Proteínas Reguladoras y Accesorias Virales/genética , Infecciones Asintomáticas , Bases de Datos de Ácidos Nucleicos , Endocarditis/virología , Humanos , Leucemia-Linfoma de Células T del Adulto/virología , Mutación , Paraparesia Espástica Tropical/virologíaRESUMEN
To gain insight into the origin, evolution, dissemination and viral factors affecting HTLV-1-associated diseases, knowing the complete viral genome sequences is important. So far, no full-length HTLV-1 genome sequence has been reported from Iran. Here we report the complete nucleotide sequence of HTLV-1 viruses isolated from adult T cell leukemia/lymphoma (ATLL) patients from this region. The genome size of HTLV-1-MhD (Mashhad) was found to be 9036â¯bp and sequence analysis of the LTR region showed that it belongs to cosmopolitan subtype A. Comparing the sequences with isolates from another endemic area (HTLV-1ATK) revealed variations in the U3 region (~3.4%), while there was 99.1% and 97.0% similarity in R and U5 regions, respectively. The nucleotide sequences of HTLV-1 gag, pro and pol genes had a difference of 1.1% compared with HTLV-1 ATK with 16 nucleotides replaced in the gag and 27 in the pol regions. There was no variability in the amino acid sequences in the p24gag, however three residues were different in the p19gag and one in the p15gag. The nucleotide sequence of env showed a divergence of 1.5% compared to ATK with 22-nucleotide variation. The HTLV-1-MhD Tax, p13, p30, and p12 had 99.1, 100, 98.8, and 98%, respectively similarity with the prototype strain. Four amino acid changes were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. The nucleotide identity between the isolates of Mashhad and those isolated from France, Germany, China, Canada and Brazil was 99.1%, 99.2%, 97.9%, 99% and 99.3%, respectively. Four amino acid changes compared with HTLV-1ATK from Japan were detected in ORF1 and ORF2 products p12 and p30, respectively, while the p13 region showed 100% conservation. This data could provide information regarding the evolutionary history, phylogeny, origin of the virus and vaccine design.
Asunto(s)
Virus Linfotrópico T Tipo 1 Humano/genética , Leucemia-Linfoma de Células T del Adulto/virología , Sistemas de Lectura Abierta/genética , Péptido Hidrolasas/genética , Factores de Transcripción/genética , Proteínas Reguladoras y Accesorias Virales/genética , Secuencia de Aminoácidos , Secuencia de Bases , Brasil , Canadá , China , ADN Viral/genética , Femenino , Francia , Genes Virales/genética , Alemania , Humanos , Irán , Japón , Masculino , Persona de Mediana Edad , Secuencias Repetitivas de Ácidos Nucleicos/genéticaRESUMEN
Resumen La leucemia/linfoma T del adulto (LLTA) de tipo linfomatoso es un subtipo del linfoma de las células T, causado por la infección del virus linfotrópico de células T humanas tipo 1 (HTLV-1); el cual genera una integración proviral en el ADN del hospedero y expansión clonal de linfocitos T. Presentamos el caso de una mujer de 20 años que desarrolló linfadenopatías múltiples, hepatoesplenomegalia y fiebre, con serología positiva para HTLV-1 y reacción de polimerasa en cadena (RPC) con la integración proviral en el ADN del hospedero. La inmunohistoquímica en un ganglio linfático fue positiva para células T CD4+ y CD8+. La LLTA ha sido descrito en todas las áreas endémicas del HTLV-1; sin embargo, existen diferencias en la edad de presentación según la región: 40 a 50 años en América del Sur y 60 años en Japón. Presentamos uno de los pocos casos reportados de LLTA de tipo linfomatoso en adultos jóvenes.
Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.
Asunto(s)
Humanos , Femenino , Adulto Joven , Virus Linfotrópico T Tipo 1 Humano , Infecciones por HTLV-I/virología , Leucemia-Linfoma de Células T del Adulto/virología , Leucemia-Linfoma Linfoblástico de Células Precursoras/virología , Ensayo de Inmunoadsorción Enzimática , Resultado Fatal , Linfadenopatía/virologíaRESUMEN
Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission.
Asunto(s)
Infecciones por HTLV-I/complicaciones , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Fallo Hepático Agudo/etiología , Resultado Fatal , Humanos , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Persona de Mediana EdadRESUMEN
La falla hepática aguda es el desarrollo de injuria hepática severa con deterioro de la función de síntesis y encefalopatía. Dentro de la variedad de causas, las infiltraciones neoplásicas representan menos del 0,5%. Presentamos el caso de un paciente varón HTLV1 positivo que debuta con una clínica de hepatitis aguda, siendo posteriormente diagnosticado con diseminación de linfoma/leucemia de células T del adulto. Desafortunadamente el paciente presentó deterioro rápido y progresivo de la función hepática, falleciendo a los pocos días de la hospitalización
Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/ lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission
Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Infecciones por HTLV-I/complicaciones , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Fallo Hepático Agudo/etiología , Leucemia-Linfoma de Células T del Adulto/complicaciones , Leucemia-Linfoma de Células T del Adulto/virología , Resultado FatalRESUMEN
BACKGROUND: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. CASE REPORT: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. TREATMENT AND OUTCOME: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. CLINICAL RELEVANCE: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).
ANTECEDENTES: La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrucosos. CASO CLÍNICO: Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2. TRATAMIENTO Y RESULTADO: La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció. RELEVANCIA CLINICA: La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrucosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).
Asunto(s)
Carcinoma Verrugoso/diagnóstico , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfocitos T CD4-Positivos , Carcinoma Verrugoso/etiología , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Resultado Fatal , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/virología , Persona de Mediana Edad , Prednisona/uso terapéutico , Factores de Riesgo , Vincristina/uso terapéuticoRESUMEN
Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.
Asunto(s)
Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Resultado Fatal , Femenino , Humanos , Leucemia-Linfoma de Células T del Adulto/virología , Persona de Mediana Edad , UruguayRESUMEN
La leucemia/linfoma T del adulto pertenece al grupo de neoplasias T maduras y constituye una entidad clínica de baja incidencia. Su etiopatogenia se asocia a la infección por el virus linfotrópico humano 1. En Uruguay se registra una incidencia muy baja de infección por este virus y no se ha comunicado a la fecha ningún caso de leucemia/linfoma T del adulto. Presentamos el caso de una inmigrante de Perú, quien se presentó con linfocitosis sostenida, múltiples parasitosis intestinales y compromiso cutáneo. El diagnóstico fue tardío y la paciente falleció antes de iniciar tratamiento oncoespecífico. Destacamos la importancia de la sospecha clínica de esta entidad y el estudio de la serología para el virus, en particular en casos, como el nuestro, procedentes de área endémica.
Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Uruguay , Leucemia-Linfoma de Células T del Adulto/virología , Resultado FatalRESUMEN
BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive neoplasm of T-lymphocytes associated with human T-lymphotropic virus type I (HTLV-1) infection. As HTLV-1 is endemic in native ethnics in South America, and its infection leads to several chronic diseases as ATLL with poor prognosis, we aimed to present three ATLL cases and to review current literature. CASE REPORTS: Two cases were from the mountains of Peru, while one was from an endemic harbor of the country. An acute ATLL patient presented with multipapular infiltration of the skin and died 2 weeks after admission because of septic shock. The two chronic ATLL patients presented with erythematous plaques and erythroderma. They had swollen lymph nodes, lymphocytosis, and atypical lymphocytes on blood smear, with normal biochemical results. They both passed away a few months after diagnosis. COMMENTS: ATLL is developed after years of HTLV-1 carrier status; therefore, physicians should know the principal clinical and laboratory findings in order to make prompt diagnosis. Prognosis is still poor in aggressive and indolent variants, with survival rates from months to a few years. Treatment based on chemotherapy, antiretroviral, and allogeneic stem cell transplantation are improving survival rates but with limited results.
Asunto(s)
Anticuerpos Antivirales/sangre , Virus Linfotrópico T Tipo 1 Humano/inmunología , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Anciano , Anciano de 80 o más Años , Resultado Fatal , Femenino , Hospitales , Humanos , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/patología , Leucemia-Linfoma de Células T del Adulto/virología , Masculino , Persona de Mediana Edad , Perú , PronósticoRESUMEN
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.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Enfermedad de Hodgkin/patología , Infecciones por HTLV-I/patología , Leucemia-Linfoma de Células T del Adulto/patología , Linfocitosis/patología , Biopsia , Ensayo de Inmunoadsorción Enzimática , Enfermedad de Hodgkin/virología , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/virología , Resultado Fatal , Linfocitosis/virología , Ganglios Linfáticos/patologíaRESUMEN
Abstract Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).
Resumen Antecedentes: La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrugosos. Caso clínico: Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2. Tratamiento y resultado: La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció Relevancia clinica: La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrugosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).
Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Virus Linfotrópico T Tipo 1 Humano/aislamiento & purificación , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Carcinoma Verrugoso/diagnóstico , Vincristina/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Prednisona/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma de Células T del Adulto/virología , Linfocitos T CD4-Positivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Doxorrubicina/uso terapéutico , Factores de Riesgo , Resultado Fatal , Carcinoma Verrugoso/etiología , Ciclofosfamida/uso terapéuticoRESUMEN
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.