Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 189
Filtrar
Más filtros

Intervalo de año de publicación
1.
Blood ; 129(9): 1134-1142, 2017 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-28115371

RESUMEN

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 ∼50% 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 Joven
2.
Curr Oncol Rep ; 21(5): 40, 2019 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-30919085

RESUMEN

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 , Pronóstico
3.
Br J Haematol ; 180(6): 919-924, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29441563

RESUMEN

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 T
4.
Kidney Int ; 91(3): 691-698, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27998645

RESUMEN

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 Tratamiento
5.
Dokl Biochem Biophys ; 467(1): 85-8, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27193704

RESUMEN

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)J
7.
J Zoo Wildl Med ; 46(3): 580-2, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26352964

RESUMEN

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 terapéutico
9.
Pediatr Emerg Care ; 28(8): 807-9, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22863823

RESUMEN

Pharyngitis is a common clinical complaint for children and accounts for 3.1% of all visits to selected ambulatory care settings. Most children with pharyngitis have benign, self-limited disease with infrequent complications such as peritonsillar abscess, mastoiditis, or lymphadenitis. Recent studies have touted the benefits of steroids in the treatment of children with pharyngitis for pain control. These studies do not address the potential life-threatening complication of steroids in patients with pharyngitis or lymphadenopathy in the setting of undiagnosed acute lymphocytic leukemia (ALL) or lymphoma. We report 4 cases of children treated with steroids for pharyngitis or adenitis that subsequently were diagnosed with ALL or lymphoma. If steroids are to be used in children with pharyngitis or adenitis, the following recommendations should be strongly considered: Careful history and physical examination should be obtained. Presence of hepatosplenomegaly or lymphadenopathy outside the cervical region should raise suspicions regarding an underlying malignancy. Normal results of complete blood cell count in the setting of clear cut pharyngitis with exudates and a lack of significant adenopathy essentially rules out the diagnosis of ALL. Because traditional analgesics are available, which do not affect the curability of ALL or lymphoma, the routine use of steroids in pharyngitis in children should be considered only in rare circumstances.


Asunto(s)
Glucocorticoides/efectos adversos , Leucemia de Células T/diagnóstico , Linfadenitis/tratamiento farmacológico , Faringitis/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Recuento de Células Sanguíneas , Médula Ósea/patología , Niño , Preescolar , Femenino , Glucocorticoides/administración & dosificación , Hepatomegalia , Humanos , Leucemia de Células T/terapia , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Esplenomegalia
10.
Br J Haematol ; 153(4): 451-85, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21480860

RESUMEN

The peripheral T-cell neoplasms are a biologically and clinically heterogeneous group of rare disorders that result from clonal proliferation of mature post-thymic lymphocytes. Natural killer (NK) cell neoplasms are included in this group. The World Health Organization classification of haemopoietic malignancies has divided this group of disorders into those with predominantly leukaemic (disseminated), nodal, extra-nodal or cutaneous presentation. They usually affect adults and are more commonly reported in males than in females. The median age at diagnosis is 61 years with a range of 17-90 years. Although some subtypes may follow a relatively benign protracted course most have an aggressive clinical behaviour and poor prognosis. Excluding anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), which has a good outcome, 5-year survival for other nodal and extranodal T-cell lymphomas is about 30%. Most patients present with unfavourable international prognostic index scores (>3) and poor performance status. The rarity of these diseases and the lack of randomized trials mean that there is no consensus about optimal therapy for T- and NK-cell neoplasms and recommendations in this guideline are therefore based on small case series, phase II trials and expert opinion.


Asunto(s)
Células Asesinas Naturales , Leucemia de Células T/terapia , Linfoma de Células T/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Medicina Basada en la Evidencia/métodos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Incidencia , Leucemia de Células T/diagnóstico , Leucemia de Células T/epidemiología , Linfoma de Células T/diagnóstico , Linfoma de Células T/epidemiología , Linfoma de Células T Periférico/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Adulto Joven
11.
Pediatr Blood Cancer ; 56(3): 467-9, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21225930

RESUMEN

Acute bilineal leukemias are rare and are commonly associated with t(9;22) and MLL abnormalities. Herein, we report a pediatric case of bilineal T/myeloid acute leukemia associated with del (9q)(q13q22) and TLX3/BCL11B fusion due to the cryptic t(5;14)(q35;32). FISH studies confirmed the TLX3/BCL11B fusion in both the myeloid and lymphoid blasts, while the 9q deletion was restricted to the lymphoid component. Optimal therapy for such patients remains controversial and it is not clear if they should be treated with ALL or AML-based chemotherapeutic regimens. Our patient has been in extended remission following ALL-based chemotherapy and a matched unrelated cord blood transplant. Inc.


Asunto(s)
Cromosomas Humanos Par 9/genética , Proteínas de Homeodominio/genética , Leucemia Bifenotípica Aguda/terapia , Leucemia Mieloide Aguda/terapia , Leucemia de Células T/terapia , Proteínas de Fusión Oncogénica/genética , Proteínas Represoras/genética , Proteínas Supresoras de Tumor/genética , Antineoplásicos/uso terapéutico , Trasplante de Médula Ósea , Niño , Cromosomas Humanos Par 22/genética , Terapia Combinada , Humanos , Hibridación Fluorescente in Situ , Leucemia Bifenotípica Aguda/diagnóstico , Leucemia Bifenotípica Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia de Células T/diagnóstico , Leucemia de Células T/genética , Masculino , ARN Mensajero/genética , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia , Translocación Genética/genética , Resultado del Tratamiento
12.
Pediatr Dermatol ; 28(5): 535-7, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21895759

RESUMEN

An 8-year-old boy presented with a widespread cutaneous eruption featuring macules, papules, nodules, and ulcers. The histologic infiltrate showed T lymphoblasts, but there was no sign of systemic involvement, so aleukemic leukemia cutis was diagnosed. Two months later, he developed leukemia in peripheral blood and bone marrow that was characterized as T-cell acute lymphoblastic leukemia.


Asunto(s)
Leucemia de Células T/diagnóstico , Lesiones Precancerosas/diagnóstico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico , Neoplasias Cutáneas/diagnóstico , Niño , Humanos , Leucemia de Células T/patología , Masculino , Lesiones Precancerosas/patología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Neoplasias Cutáneas/patología , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patología
13.
Acta Cardiol ; 66(2): 251-3, 2011 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21591587

RESUMEN

Cardiac tamponade is a life-threatening emergency that has to be promptly recognised. We report the case of a young adult patient with an acute cardiac tamponade as a rare presenting symptom of T-cell acute leukaemia. An emergency pericardiocentesis was performed with immediate relief of the symptoms. The aetiology was diagnosed on the basis of the serological hyperleucocytosis and the anatomopathological analysis of the pericardial fluid. The patient was subsequently referred for chemotherapy. Acute leukaemia presenting with pericardial tamponade as a first sign is rare, and described only in a few case reports. Furthermore, we discuss the diagnostic and therapeutic measures of haemodynamic unstable cardiac tamponade.


Asunto(s)
Taponamiento Cardíaco/etiología , Leucemia de Células T/complicaciones , Adulto , Taponamiento Cardíaco/diagnóstico , Diagnóstico Diferencial , Ecocardiografía , Femenino , Humanos , Leucemia de Células T/diagnóstico , Radiografía Torácica
14.
J Vet Diagn Invest ; 33(4): 792-796, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33884946

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 , Pronóstico
15.
Appl Immunohistochem Mol Morphol ; 28(7): 508-512, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-31290784

RESUMEN

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 Retrospectivos
16.
Blood Cells Mol Dis ; 42(1): 57-63, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-18842429

RESUMEN

The World Health Organization classification of mature T-cell lymphoproliferative disorders, combines clinical, morphological and immunophenotypic data. The latter is a major contributor to the classification, as well as to the understanding of the malignant T-cell behavior. The fact that T-cell migration is regulated by chemokines should, in theory, enable us to identify tissue tropism and organ involvement by neoplastic T-cells by monitoring chemokine receptor surface expression. To address this issue we compared the expression of several early and late inflammatory, homeostatic, and organ specific chemokine receptors on blood T-cells from normal individuals and patients with T-cell large granular lymphocytic leukemia and peripheral T-cell lymphoma. T-cell large granular lymphocytic leukemia cells mainly express late inflammatory chemokine receptors (CXCR1 and CXCR2), whereas peripheral T-cell lymphoma cells usually express one or more organ homing receptors (CCR4, CCR6 and CCR7). Nevertheless, no clear correlation was found between CCR4 and CCR7 expression and skin and lymph node involvement, respectively. Compared to their normal counterparts, lymphoma T-cells displayed an exaggerated CCR4 expression, whereas leukemic T-cells had abnormally high CXCR1 and CXCR2 expression. Further analysis revealed that, in leukemia patients, the percentage of neoplastic cells expressing CCR5 correlates directly with lymphocytosis. In addition, in the case of CD8 T-cell leukemia patients, an inverse correlation with neutropenia was found. In lymphoma patients, higher CCR4 and CCR7 expression is accompanied by lower to absent CCR5 expression.


Asunto(s)
Leucemia de Células T/clasificación , Leucemia de Células T/diagnóstico , Linfoma de Células T/clasificación , Linfoma de Células T/diagnóstico , Receptores de Quimiocina/inmunología , Subgrupos de Linfocitos T/inmunología , Citocinas/inmunología , Humanos , Leucemia de Células T/inmunología , Linfoma de Células T/inmunología , Receptores de Quimiocina/análisis , Subgrupos de Linfocitos T/patología
17.
J Leukoc Biol ; 83(1): 220-2, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17962369

RESUMEN

Fas (TNFRSF6/Apo-1/CD95) is a type I transmembrane receptor, which mediates apoptosis. Fas gene mutations, aberrant transcripts, and abundant expression of Fas have been reported in adult T cell leukemia (ATL). To further elucidate the role of Fas in ATL pathogenesis, we investigated whether the -670 FAS promoter A/G polymorphism (STAT1-binding site) might contribute to susceptibility and clinical outcome in ATL. Thirty-one patients with ATL, 33 healthy, human T lymphotropic virus type 1-infected individuals, and 70 healthy, uninfected controls were genotyped for the FAS -670 polymorphism by PCR-restriction fragment-length polymorphism. The AA genotype was significantly over-represented in ATL patients in comparison with healthy controls (P=0.006), as well as asymptomatics (P=0.037), corresponding to an odds ratio (OR) of 3.79 [95% confidence intervals (CI; 1.28-11.41)] and 4.58 [95% CI (1.13-20.03)], respectively. The AA group also comprised significantly more aggressive (acute and lymphoma) clinical subtypes [P=0.012; OR=8.40; 95% CI (1.60-44.12)]. In addition, we observed a statistically significant association between GG genotype and survival (log rank test, P=0.032). Finally, IFN-gamma-induced but not basal FAS mRNA levels were increased significantly (P=0.049) in PBMCs from AA versus GG individuals, demonstrating the IFN-dependent functionality of the -670 polymorphism. In conclusion, our results demonstrate that a functional Fas promoter polymorphism is significantly associated to susceptibility, clinical manifestation, and survival in ATL.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Leucemia de Células T/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Receptor fas/genética , Estudios de Seguimiento , Genotipo , Infecciones por HTLV-I/inmunología , Infecciones por HTLV-I/virología , Humanos , Interferón gamma/farmacología , Leucemia de Células T/diagnóstico , Leucemia de Células T/virología , Leucocitos Mononucleares/efectos de los fármacos , ARN Mensajero/genética , Factores de Riesgo , Tasa de Supervivencia , Receptor fas/inmunología
18.
Cell Death Dis ; 9(10): 1013, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30598523

RESUMEN

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 Supervivencia
19.
Eur Respir J ; 31(6): 1368-72, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18515560

RESUMEN

The present study describes an adult male who has had recurrent episodes of pulmonary infiltrates with severe acute respiratory failure over a period of 10 yrs. Clinical and pathological characteristics revealed bronchiolitis obliterans with organising pneumonia (BOOP) that responded dramatically to prednisone. BOOP is characterised by inflammation of the bronchioles and surrounding tissue in the lungs. It can mimic infectious pneumonia but diagnosis is suspected when there is no response to multiple antibiotic treatment, and blood and sputum cultures are negative for microorganisms. A high proportion of double-positive (DP)-T-cells was detected in peripheral blood and in bronchoalveolar lavage, expressing CD4 and CD8alphabeta heterodimer with memory phenotype. These DP-T-lymphocytes expressed specific homing molecules that could explain their tropism to lung tissue, giving rise to the clinical symptoms. The patient did not present organomegaly, lymphadenopathy, lymphocytosis or other features of malignancy. However, T-cell receptor Vbeta chain analysis indicated clonal rearrangement, and cytogenetic studies displayed chromosomic alterations that were similar to clonal proliferation observed in ataxia-telangiectasia and T-prolymphocytic leukaemia. The findings suggest a smouldering form of lymphoproliferation, the first sign of which was bronchiolitis obliterans organising pneumonia requiring constant corticoid treatment.


Asunto(s)
Neumonía en Organización Criptogénica/complicaciones , Leucemia de Células T/complicaciones , Leucemia de Células T/diagnóstico , Adulto , Antiinflamatorios/uso terapéutico , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , Neumonía en Organización Criptogénica/sangre , Neumonía en Organización Criptogénica/tratamiento farmacológico , Humanos , Leucemia de Células T/clasificación , Masculino , Prednisolona/uso terapéutico
20.
Leuk Res ; 32(1): 45-8, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17544120

RESUMEN

We report on the clinico-biological characteristics of 20 cases of gammadelta T cell large granular lymphocyte (LGL) leukemia. All the data were compared to that of 196 cases with alphabeta T cell subtype, which represents the majority of T cell LGL leukemias. Clinical findings were quite similar in the two groups regarding age, sex ratio, recurrent infections, and association with auto-immune diseases especially rheumatoid arthritis. Gammadelta LGL predominantly expressed a CD3+/CD4-/CD8+/CD16+/CD57+ phenotype, in 50% of cases. Clinical outcome was favorable for these patients with overall survival of 85% at 3 years. Fifty percent of gammadelta patients required treatment and the response to therapy was estimated at 55%. gammadelta and alphabeta T cell LGL leukemia harbor a very similar clinico-biological behavior and represent part of an antigen-driven T cell lymphoproliferation.


Asunto(s)
Leucemia de Células T/diagnóstico , Receptores de Antígenos de Linfocitos T gamma-delta , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/complicaciones , Células Clonales , Femenino , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Humanos , Inmunofenotipificación , Leucemia de Células T/inmunología , Leucopenia/diagnóstico , Masculino , Persona de Mediana Edad , Receptores de Antígenos de Linfocitos T alfa-beta , Esplenomegalia/diagnóstico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA