RESUMEN
An 8-y-old spayed female Beagle dog was presented with peripheral lymphadenomegaly. Lymph node cytology and flow cytometry led to the diagnosis of large B-cell lymphoma (LBCL). We detected minimal percentages of LBCL cells in peripheral blood and bone marrow samples. However, a monomorphic population of neoplastic cells different from those found in the lymph node was found in the bone marrow. T-cell acute lymphoblastic leukemia was suspected based on flow cytometric immunophenotyping. PCR for antigen receptor rearrangement (PARR) revealed clonal rearrangement of both B-cell and T-cell receptors, and the presence of both neoplastic clones in the lymph node, peripheral blood, and bone marrow. The dog was treated with multi-agent chemotherapy but died 46 d following diagnosis. Tumor staging and patient classification are needed to accurately establish a prognosis and select the most appropriate therapeutic protocol.
Asunto(s)
Enfermedades de los Perros/diagnóstico , Leucemia de Células T/veterinaria , Linfoma de Células B Grandes Difuso/veterinaria , Estadificación de Neoplasias/veterinaria , Leucemia-Linfoma Linfoblástico de Células Precursoras/veterinaria , Animales , Antineoplásicos/administración & dosificación , Enfermedades de los Perros/patología , Perros , Resultado Fatal , Femenino , Citometría de Flujo/veterinaria , Inmunofenotipificación/veterinaria , Leucemia de Células T/diagnóstico , Leucemia de Células T/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , PronósticoAsunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Trasplante de Riñón , Leucemia de Células T , Receptores de Trasplantes , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/epidemiología , Humanos , Trasplante de Riñón/efectos adversos , Leucemia de Células T/diagnóstico , Leucemia de Células T/epidemiología , PronósticoRESUMEN
We aim to evaluate the degree of agreement between immunohistochemistry (IHC) and flow cytometry (FC) in the diagnosis of malignant hematologic diseases, mainly lymphomas. A total of 260 bone marrow biopsies, 255 bone marrow aspirates, and 5 other suspensions of 260 patients used for diagnosis of a hematologic malignancy between 2009 and 2012 with both, IHC and FC, were retrospectively analyzed. Overall there is a substantial degree of agreement (κ=0.69) between IHC and FC. Chronic lymphocytic leukemia/small lymphocytic lymphoma, mature T-cell neoplasms, acute leukemias, and myelodysplastic syndromes had the highest concurrence rates (>80%). In nonconcordant cases, an IHC provided diagnosis in 25.4%, and an FC in 4.6%. Lymphomas were diagnosed by an IHC only in 51% of the cases. Both methods have good concurrence rates and are complementary. An IHC has the advantage of combining markers, morphology, and tissue immunoarchitecture, which is beneficial in the diagnosis of lymphomas. An FC is required in leukemias as it is faster and plays an important role in minimal residual disease.
Asunto(s)
Citometría de Flujo/métodos , Neoplasias Hematológicas/diagnóstico , Inmunohistoquímica/métodos , Linfoma/diagnóstico , Biopsia , Médula Ósea/patología , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patología , Humanos , Inmunofenotipificación , Leucemia/diagnóstico , Leucemia/metabolismo , Leucemia/patología , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Leucemia de Células T/diagnóstico , Leucemia de Células T/metabolismo , Leucemia de Células T/patología , Linfoma/metabolismo , Linfoma/patología , Linfoma de Células B/diagnóstico , Linfoma de Células B/metabolismo , Linfoma de Células B/patología , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Estudios RetrospectivosAsunto(s)
Dermatitis/patología , Progresión de la Enfermedad , Queratodermia Palmoplantar/patología , Leucemia de Células T/patología , Prurito/patología , Anciano de 80 o más Años , Alemtuzumab/uso terapéutico , Biopsia con Aguja , Enfermedad Crónica , Dermatitis/complicaciones , Dermatitis/diagnóstico , Dermatitis/tratamiento farmacológico , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Queratodermia Palmoplantar/complicaciones , Queratodermia Palmoplantar/diagnóstico , Queratodermia Palmoplantar/tratamiento farmacológico , Leucemia de Células T/diagnóstico , Leucemia de Células T/terapia , Masculino , Persona de Mediana Edad , Prurito/complicaciones , Prurito/diagnóstico , Prurito/tratamiento farmacológico , Medición de Riesgo , Muestreo , Índice de Severidad de la Enfermedad , Trasplante de Células Madre/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE OF REVIEW: Peripheral natural killer (NK) and T cell neoplasms comprise approximately 10-15% of non-Hodgkin lymphomas. There are 27 different subtypes of peripheral NK and T cell neoplasms, each of which is relatively uncommon. Treatment has been largely extrapolated from case series, retrospective reports, and paradigms developed for the aggressive B cell lymphomas. This review explores the current knowledge of the characteristics, outcome, and treatment of CNS T cell and NK neoplasms. RECENT FINDINGS: Primary and secondary CNS NK and T cell malignancies confer significant morbidity and poor prognosis. Despite clinical heterogeneity between the 27 subtypes, high-dose methotrexate-based regimens seem most effective overall. The role of prophylaxis against secondary CNS involvement remains controversial. Autologous stem cell transplant and immunotherapy are potential for promising future therapies. Current understanding of incidence, outcome, and optimal treatment strategies for CNS T cell and NK neoplasms is limited, in large part due to their diversity and rarity. Prognosis is poor, except in a few reports of long-term survival in patients most often treated with combination therapy including high-dose methotrexate. A future prospective study on treatment and outcome in CNS T cell and NK neoplasms is needed to better define these diseases.
Asunto(s)
Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Células Asesinas Naturales/patología , Linfocitos T/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/patología , Terapia Combinada , Humanos , Leucemia de Células T/diagnóstico , Leucemia de Células T/mortalidad , Leucemia de Células T/patología , Leucemia de Células T/terapia , Linfoma no Hodgkin/diagnóstico , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/terapia , Metotrexato/uso terapéutico , PronósticoRESUMEN
Glucocorticoids (GCs) are widely used drugs in the treatment of lymphoid malignancies; resistance of GCs in lymphocytes confers poor prognosis and the mechanisms are poorly understood. Here, we found T-acute lymphoblastic leukemia (T-ALL) cells acquire resistance to dexamethasone (DEX)-mediated killing through abnormal activation of Akt, resulting in inhibition of the FoxO3a/Bim pathway. The resistant state was reported to be associated with increased glycolysis, NOTCH1 activating mutations and activated PI3K/ serum GS regulated kinases (SGK) pathway. Use of aforementioned pathway inhibitors blocked FoxO3a-phosphorylation and partially improved DEX-mediated killing of GC-resistant T-ALL cells, further revealing the essential role of the FoxO3a/Bim pathway in the development of GC resistance. Inhibition of Akt is most effective at restoring sensitivity to DEX of GC-resistant lymphocytes in vitro and in vivo, but shows significant hepatotoxicity in vivo. A significantly elevated expression of Akt2 not Akt1 in intrinsically, secondarily GC-resistant lymphocytes and relapsed/refractory ALL patients implicates a more specific target for GC resistance. Mechanistically, Akt2 has a stronger binding capacity with FoxO3a compared to Akt1, and acts as a direct and major negative regulator of FoxO3a activity driving GC resistance. Pharmacologic inhibition of Akt2 more effectively restores sensitivity to GCs than inhibition of Akt1 in vitro, shows higher synergistic effect acting with DEX, and reverses GC resistance in GC-resistant T- or B- lymphoid tumors in vivo with reduced liver toxicity. In summary, these results suggest that Akt2 might serve as a more direct and specific kinase mediating GC resistance through FoxO3a/Bim signaling pathway, and Akt2 inhibition may be explored as a promising target for treating GC-resistant hematopoietic malignancies.
Asunto(s)
Proteína 11 Similar a Bcl2/metabolismo , Resistencia a Antineoplásicos , Proteína Forkhead Box O3/metabolismo , Glucocorticoides/farmacología , Leucemia de Células T/diagnóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Dexametasona/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Glucocorticoides/uso terapéutico , Humanos , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/mortalidad , Leucemia de Células T/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ratones , Ratones Desnudos , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Tasa de SupervivenciaRESUMEN
CASE PRESENTATION: A 61-year-old Caribbean man presented to the ED with dyspnea that had progressed over the previous week with associated cough and high fevers. Four days prior to admission, his primary care physician noted oral thrush and obtained a chest radiograph that revealed a right middle lobe infiltrate. He was prescribed levofloxacin and clotrimazole. Despite therapy, his symptoms progressed. He had an 11 pack-year smoking history and hypertension but had been in good health. He denied recent travel, alcohol or illicit drug use, or high-risk sexual behaviors, and his only previous medicine was amlodipine. Institutional review board approval was not obtained for this case report, as all patient data are anonymous and obtained during routine patient care activities.
Asunto(s)
Anticuerpos Antivirales/análisis , Infecciones por Deltaretrovirus/complicaciones , Leucemia de Células T/complicaciones , Virus Linfotrópico T Tipo 1 de los Primates/inmunología , Insuficiencia Respiratoria/etiología , Infecciones Tumorales por Virus/complicaciones , Biopsia , Broncoscopía , Región del Caribe , Infecciones por Deltaretrovirus/diagnóstico , Infecciones por Deltaretrovirus/virología , Diagnóstico Diferencial , Humanos , Leucemia de Células T/diagnóstico , Leucemia de Células T/virología , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/diagnóstico , Tomografía Computarizada por Rayos X , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/virologíaAsunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia de Células T/diagnóstico , Ganglios Linfáticos/patología , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Biopsia , Células de la Médula Ósea/patología , Diagnóstico Diferencial , Errores Diagnósticos/prevención & control , Resultado Fatal , Técnicas Histológicas , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/patología , Ganglios Linfáticos/ultraestructura , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Advances in the classification of acute leukaemias have led to improved outcomes for a substantial fraction of patients. However, chemotherapy resistance remains a major problem for specific subsets of acute leukaemias. Here, we propose that a molecularly distinct subtype of acute leukaemia with shared myeloid and T cell lymphoblastic features, which we term acute myeloid/T-lymphoblastic leukaemia (AMTL), is divided across 3 diagnostic categories owing to variable expression of markers deemed to be defining of myeloid and T-lymphoid lineages, such as myeloperoxidase and CD3. This proposed diagnostic group is supported by (i) retained myeloid differentiation potential during early T cell lymphoid development, (ii) recognition that some cases of acute myeloid leukaemia (AML) harbour hallmarks of T cell development, such as T-cell receptor gene rearrangements and (iii) common gene mutations in subsets of AML and T cell acute lymphoblastic leukaemia (T-ALL), including WT1, PHF6, RUNX1 and BCL11B. This proposed diagnostic entity overlaps with early T cell precursor (ETP) T-ALL and T cell/myeloid mixed phenotype acute leukaemias (MPALs), and also includes a subset of leukaemias currently classified as AML with features of T-lymphoblastic development. The proposed classification of AMTL as a distinct entity would enable more precise prospective diagnosis and permit the development of improved therapies for patients whose treatment is inadequate with current approaches.
Asunto(s)
Leucemia Mielomonocítica Aguda , Leucemia de Células T , Humanos , Leucemia Mielomonocítica Aguda/clasificación , Leucemia Mielomonocítica Aguda/diagnóstico , Leucemia Mielomonocítica Aguda/genética , Leucemia Mielomonocítica Aguda/terapia , Leucemia de Células T/clasificación , Leucemia de Células T/diagnóstico , Leucemia de Células T/genética , Leucemia de Células T/terapia , Células Mieloides , Proteínas de Neoplasias/genética , Células Precursoras de Linfocitos TRESUMEN
Flow cytometry is ideally suited for the immunophenotypic analysis of T-cell neoplasia. This article covers the spectrum of flow cytometric findings associated with frequently encountered benign and neoplastic T-cell populations and details the most common immunophenotypic features associated with specific neoplasms of both immature and mature T cells.
Asunto(s)
Citometría de Flujo , Leucemia de Células T , Linfoma de Células T , Linfocitos T/citología , Humanos , Inmunofenotipificación , Leucemia de Células T/clasificación , Leucemia de Células T/diagnóstico , Linfoma de Células T/clasificación , Linfoma de Células T/diagnósticoRESUMEN
A microfluidic structured-dual electrodes sensor comprising of a pair of screen printed carbon electrodes was fabricated to detect acetylcholine, where one of them was used for an enzyme reaction and another for a detection electrode. The former was coated with gold nanoparticles and the latter with a porous gold layer, followed by electropolymerization of 2, 2:5,2-terthiophene-3-(p-benzoic acid) (pTTBA) on both the electrodes. Then, acetylcholinesterase was covalently attached onto the reaction electrode, and hydrazine and choline oxidase were co-immobilized on the detection electrode. The layers of both modified electrodes were characterized employing voltammetry, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and quartz crystal microscopy. After the modifications of both electrode surfaces, they were precisely faced each other to form a microfluidic channel structure, where H2O2 produced from the sequential enzymatic reactions was reduced by hydrazine to obtain the analytical signal which was analyzed by the detection electrode. The microfluidic sensor at the optimized experimental conditions exhibited a wide dynamic range from 0.7nM to 1500µM with the detection limit of 0.6 ± 0.1nM based on 3s (S/N = 3). The biomedical application of the proposed sensor was evaluated by detecting acetylcholine in human plasma samples. Moreover, the Ca2+-induced acetylcholine released in leukemic T-cells was also investigated to show the in vitro detection ability of the designed microfluidic sensor. Interference due to the real component matrix were also studied and long term stability of the designed sensor was evaluated. The analytical performance of the designed sensor was also compared with commercially available ACh detection kit.
Asunto(s)
Acetilcolina/aislamiento & purificación , Técnicas Biosensibles/métodos , Leucemia de Células T/diagnóstico , Nanopartículas del Metal/química , Acetilcolina/metabolismo , Acetilcolinesterasa/química , Calcio/química , Calcio/metabolismo , Técnicas Electroquímicas , Humanos , Leucemia de Células T/patología , Límite de Detección , Microfluídica , Linfocitos T/química , Linfocitos T/patologíaRESUMEN
T-cell acute lymphoblastic leukemia (ALL) is a rare disease in adults with inferior survival outcomes compared with those seen in pediatric patients. Although potentially curable with â¼50% survival at 5 years, adult patients with relapsed disease have dismal outcomes with <10% of patients surviving long term. This review will discuss the diagnosis and management of adult patients with newly diagnosed T-cell ALL with an emphasis on the immunophenotypic and genetic analyses required to assign prognosis, risk stratify, and guide post-remission therapy. The evidence for the main components of complex T-cell ALL treatment regimens is described. The importance of monitoring minimal residual disease is emphasized, with a discussion of the different methods used. The results of hematopoietic cell transplantation are analyzed, and recommendations made about which patients should be considered for this intervention. The treatment of the adolescent and young adult group is delineated, and the role of using "pediatric-inspired" regimens in older adults considered. We also describe the current data and potential future options for the use of novel therapies, including nelarabine and γ-secretase inhibitors, in adult patients with T-cell ALL.
Asunto(s)
Leucemia de Células T/diagnóstico , Leucemia de Células T/terapia , Adolescente , Adulto , Femenino , Humanos , Leucemia de Células T/genética , Masculino , Adulto JovenRESUMEN
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13.7%). Among patients 50 and older, the prevalence of monoclonal gammopathy was 21%, which is approximately five-fold higher than the 4.2% expected rate in this population. Fifteen patients had monoclonal gammopathy of undetermined significance, one had multiple myeloma, one with smoldering myeloma, two had POEMS syndrome, and one had T-cell lymphocytic leukemia. Renal biopsy was performed in 15 cases, of which six showed thrombi, 11 showed mesangiolysis, and all showed double contours along glomerular capillary walls. Acute tubular injury was present in 12 cases. Treatment options were varied and included therapeutic plasma exchange in 11 patients. Ten patients progressed to end-stage renal disease, of which two received kidney transplant. Thus, our study shows an unexpectedly high prevalence of monoclonal gammopathy in patients with TMA, suggesting a potential pathogenetic mechanism. This study underscores the importance of evaluating for a monoclonal gammopathy in patients with TMA as well as the potential for targeting the underlying hematologic disorder as an approach to treating TMA.
Asunto(s)
Riñón , Leucemia de Células T/epidemiología , Mieloma Múltiple/epidemiología , Síndrome POEMS/epidemiología , Paraproteinemias/epidemiología , Microangiopatías Trombóticas/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Biopsia , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Inmunosupresores/uso terapéutico , Riñón/patología , Riñón/fisiopatología , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Leucemia de Células T/diagnóstico , Leucemia de Células T/terapia , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/terapia , Síndrome POEMS/diagnóstico , Síndrome POEMS/terapia , Paraproteinemias/diagnóstico , Paraproteinemias/inmunología , Paraproteinemias/terapia , Intercambio Plasmático , Prevalencia , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/terapia , Factores de Tiempo , Resultado del TratamientoRESUMEN
Aberrant hypermethylation of tumor suppressor genes is known to play an important role in the development of many tumors, and aberrant DNA hypermethylation was recently identified in hematologic malignancies, where it is thought to hold relevance in leukemogenesis. Here, we report that there are differences in the DNA methylation patterns seen in normal peripheral blood and two T-cell leukemia cell lines. We identify nine genes (CLEC4E, CR1, DBC1, EPO, HAL-DOA, IGF2, IL12B, ITGA1, and LMX1B) that are significantly hypermethylated in T-cell leukemias cell lines, and suggest that aberrant hypermethylation of these normally unmethylated genes may induce their transcriptional and expressional silencing. Furthermore, we observed that the expression levels of DNMT1 and DNMT3a were significantly decreased by 5-aza-2'-deoxycytidine (5-Aza-dC), which is a demethylation agent known to deplete DNA methyltransferases (DNMTs) in leukemia cancer cells and restore the expression levels of their target genes in Jurkat cells. This result suggests that the overexpression of DNMTs could contribute to the development of T-cell leukemias by inducing hypermethylation of the target genes. Together, our results show that aberrant hypermethylation is an important molecular mechanism in the progression of T-cell leukemias, and thus could prove useful as a prognostic and/or diagnostic marker. Moreover, 5-Aza-dC might be a promising candidate for the treatment of T-cell leukemia.
Asunto(s)
Metilación de ADN , Silenciador del Gen , Leucemia de Células T/genética , Adulto , Células Sanguíneas , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia de Células T/diagnóstico , Leucemia de Células T/terapia , MasculinoRESUMEN
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignant neoplasm of the lymphocyte precursors that suffered malignant transformation arresting the lymphoid cell differentiation. Clinical studies revealed monoor, more rarely, oligoclonal nature of the disease. A precise identification of malignant clone markers is both the crucial stage of early diagnostics and the essential prognostic factor for therapeutic treatment. Here we present an improved system for unbiased detection of lymphoblastic clones in bone marrow aspirates of T-ALL patients. The system based on multiplex PCR of rearranged T-cell receptor locus (TRB) and straightforward sequencing of the resulted PCR fragments. Testing of the system on genomic DNA from Jurkat cell line and four clinical bone marrow aspirates revealed a set of unique TRB rearrangements that precisely characterize each of tested samples. Therefore, the outcome of the system produces highly informative molecular genetic markers for further monitoring of minimal residual disease in T-ALL patients.
Asunto(s)
Reordenamiento Génico de la Cadena beta de los Receptores de Antígenos de los Linfocitos T , Leucemia de Células T/diagnóstico , Leucemia de Células T/genética , Reacción en Cadena de la Polimerasa/métodos , Médula Ósea/metabolismo , Cartilla de ADN , Electroforesis , Sitios Genéticos , Humanos , Células Jurkat , Leucemia de Células T/metabolismo , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Recombinación V(D)JRESUMEN
Kikuchi-Fujimoto disease is a benign, self-limiting condition characterized by lymphadenopathy and fever. Its diagnosis can be challenging, as the disease must be differentiated from lymphoma and systemic lupus erythematosus. Patients can present with nonspecific cutaneous lesions. Adequate clinical and histopathologic correlation can aid in the timely diagnosis of Kikuchi's disease, thus preventing the use of unnecessary diagnostic procedures and inappropriate treatments.
Asunto(s)
Adenocarcinoma/secundario , Linfadenitis Necrotizante Histiocítica/diagnóstico , Linfadenitis Necrotizante Histiocítica/patología , Leucemia de Células T/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Linfoma/diagnóstico , Diagnóstico Diferencial , Linfadenitis Necrotizante Histiocítica/tratamiento farmacológico , Humanos , Metástasis Linfática , PronósticoRESUMEN
A 17-yr-old female fallow deer presented with ataxia, inappetence, decreased fecal output, and decreased mentation. A complete blood count demonstrated leukocytosis (24.1×10(3)/µl, n=1.16-7.38×10(3)/µl), characterized by lymphocytosis (22.89×10(3)/µl, n=0.18-3.65×10(3)/µl), anemia (packed cell volume 20%, n=29.0-55.8%), decreased red blood cell count (4.1×10(3)/µl, n=6.86-14.72×10(3)/µl), and decreased hemoglobin (7.5 g/dl, n=9.4-19.2 g/dl). Numerous mature, well-differentiated lymphocytes were noted on the blood film. Despite treatment and clinical improvement, the decision was made to euthanize the deer. Histopathology identified a monomorphic population of CD3 positive, CD79a negative small lymphocytes replacing most of the hematopoietic tissue in the bone marrow without evidence of tissue invasion. Results of viral screening were negative.
Asunto(s)
Ciervos , Leucemia de Células T/veterinaria , Animales , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Dexametasona/análogos & derivados , Dexametasona/uso terapéutico , Femenino , Fluidoterapia , Lactulosa/uso terapéutico , Leucemia de Células T/diagnóstico , Leucemia de Células T/tratamiento farmacológico , Penicilina G Procaína/uso terapéuticoRESUMEN
We have previously described gene expression changes during spontaneous immortalization of T-cells, thereby identifying cellular processes important for cell growth crisis escape and unlimited proliferation. Here, we analyze the same model to investigate the role of genome-wide methylation in the immortalization process at different time points pre-crisis and post-crisis using high-resolution arrays. We show that over time in culture there is an overall accumulation of methylation alterations, with preferential increased methylation close to transcription start sites (TSSs), islands, and shore regions. Methylation and gene expression alterations did not correlate for the majority of genes, but for the fraction that correlated, gain of methylation close to TSS was associated with decreased gene expression. Interestingly, the pattern of CpG site methylation observed in immortal T-cell cultures was similar to clinical T-cell acute lymphoblastic leukemia (T-ALL) samples classified as CpG island methylator phenotype positive. These sites were highly overrepresented by polycomb target genes and involved in developmental, cell adhesion, and cell signaling processes. The presence of non-random methylation events in in vitro immortalized T-cell cultures and diagnostic T-ALL samples indicates altered methylation of CpG sites with a possible role in malignant hematopoiesis.
Asunto(s)
Transformación Celular Neoplásica/genética , Islas de CpG , Metilación de ADN , Leucemia de Células T/genética , Leucemia de Células T/patología , Linfocitos T/metabolismo , Células Cultivadas , Análisis por Conglomerados , Perfilación de la Expresión Génica , Regulación Leucémica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Leucemia de Células T/diagnóstico , Reproducibilidad de los Resultados , Linfocitos T/patologíaRESUMEN
We describe a patient with paraneoplastic autoimmune multiorgan syndrome (PAMS) secondary to a lymphoblastic T- cell lymphoma who presented with a lichenoid dermatitis and vitiligo, later developing bronchiolitis obliterans and autoimmune hepatitis. Notably, he had no detectable autoantibodies. The development of vitiligo and autoimmune hepatic involvement probably indicate a role for cytotoxic T- cell lymphocytes in the pathogenesis of this syndrome.
Asunto(s)
Autoanticuerpos , Enfermedades Autoinmunes/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Pénfigo/diagnóstico , Antineoplásicos Hormonales/administración & dosificación , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/tratamiento farmacológico , Humanos , Leucemia de Células T/sangre , Leucemia de Células T/diagnóstico , Leucemia de Células T/tratamiento farmacológico , Masculino , Síndromes Paraneoplásicos/sangre , Síndromes Paraneoplásicos/tratamiento farmacológico , Pénfigo/sangre , Pénfigo/tratamiento farmacológico , Prednisona/administración & dosificación , Adulto JovenRESUMEN
Acute pulmonary embolism (PE) is a serious complication in association with malignant diseases. We describe the successful treatment of PE applying a systemic thrombolytic therapy in a 4-year-old boy with acute lymphoblastic leukaemia. The thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) 0.1 mg/kg bodyweight per hour for six hours was continued for six days without important side effects. In particular no bleeding complications were observed. Computed tomography with contrast revealed a remarkable regression of the central PE. Without further delays the chemotherapy was resumed.