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1.
Rheumatol Int ; 41(1): 147-156, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33280072

RESUMEN

T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown.Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 109/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated.Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 109/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5-/dim on CD3+CD8+ T-lymphocytes was observed in both RA-associated T-LGLL and FS.STAT3 gene mutations or LGL counts over 2 × 109/L in RA patients are indicative of T-LGLL.


Asunto(s)
Artritis Reumatoide/complicaciones , Leucemia Linfocítica Granular Grande/genética , Adulto , Biomarcadores de Tumor/genética , Células de la Médula Ósea/patología , Diagnóstico Diferencial , Síndrome de Felty/diagnóstico , Síndrome de Felty/genética , Femenino , Humanos , Leucemia Linfocítica Granular Grande/complicaciones , Leucemia Linfocítica Granular Grande/diagnóstico , Masculino , Persona de Mediana Edad , Mutación , Neutropenia , Estudios Retrospectivos , Factor de Transcripción STAT3 , Factor de Transcripción STAT5
2.
Rheumatol Int ; 40(3): 499-506, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31707561

RESUMEN

The occurrence of diffuse large B-cell lymphoma (DLBCL) in the course of Sjogren's syndrome (SS) is considered to be equally related either to the development of DLBCL de novo or to the transformation from marginal zone lymphoma (MZL). However, the question of possible clonal relationship between MZL and DLBCL in the group of SS patients remains open. Here we present the data concerning 194 patients with lymphoma complicated SS followed up at Nasonova Research Institute of Rheumatology during the last 22 years. Molecular analysis of tumor cells was performed for 6 SS patients who had developed both MZL and DLBCL. To assess clonal relationship between each of the tumor pairs immunoglobulin heavy chain (IGH) gene rearrangements were identified according BIOMED-2 protocol by means of multiplex polymerase chain reaction followed by GeneScan fragment analysis. Despite different localization MZL and DLBCL were clonally related in five tumor pairs. The median time to transformation was 11 months (range 0-78 months). MZL and DLBCL were clonally related in most cases from our cohort of SS patients. No statistically significant difference in survival between patients with DLBCL transformed from MZL and patients with de novo DLBCL was found in the cohort of SS patients investigated.


Asunto(s)
Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Síndrome de Sjögren/complicaciones , Anciano , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/genética , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Persona de Mediana Edad , Síndrome de Sjögren/genética , Síndrome de Sjögren/patología
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