Asunto(s)
Heterocigoto , Mutación Missense , Síndrome de Noonan , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Talasemia beta , Sustitución de Aminoácidos , Niño , Humanos , Masculino , Síndrome de Noonan/sangre , Síndrome de Noonan/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/sangre , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Talasemia beta/sangre , Talasemia beta/genéticaAsunto(s)
Crioglobulinemia , Gangrena , Isquemia , Pierna , Úlcera Cutánea , Dedos del Pie , Adulto , Crioglobulinemia/complicaciones , Crioglobulinemia/patología , Femenino , Gangrena/etiología , Gangrena/patología , Humanos , Isquemia/etiología , Isquemia/patología , Pierna/irrigación sanguínea , Pierna/patología , Úlcera Cutánea/etiología , Úlcera Cutánea/patología , Dedos del Pie/irrigación sanguínea , Dedos del Pie/patologíaRESUMEN
Lymphoid enhancer-binding factor 1 (LEF1) is a neutrophilic granulopoiesis regulator whose absence is critical in congenital neutropenia. We have shown LEF1 downregulation in the CD34(+) cells of the majority of myelodysplastic syndromes (MDS) patients. LEF1 was the most significant differentially expressed gene between early and advanced MDS. Marked LEF1 downregulation was found in 27/32 patients with advanced MDS and in 6/35 patients with early MDS, and was associated with neutropenia. Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS.
Asunto(s)
Factor de Unión 1 al Potenciador Linfoide/genética , Síndromes Mielodisplásicos/genética , ARN Mensajero/análisis , Antígenos CD34/análisis , Estudios de Casos y Controles , Progresión de la Enfermedad , Regulación hacia Abajo , Perfilación de la Expresión Génica/métodos , Humanos , Inmunohistoquímica , Factor de Unión 1 al Potenciador Linfoide/análisis , Síndromes Mielodisplásicos/inmunología , Síndromes Mielodisplásicos/metabolismo , Neutropenia , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADNRESUMEN
Refractory Anemia with Ring Sideroblasts (RARS) is an acquired myelodysplastic syndrome (MDS) characterized by an excess iron accumulation in the mitochondria of erythroblasts. The pathogenesis of RARS and the cause of this unusual pattern of iron deposition remain unknown. We considered that the inherited X-linked sideroblastic anemia with ataxia (XLSA/A) might be informative for the acquired disorder, RARS. XLSA/A is caused by partial inactivating mutations of the ABCB7 ATP-binding cassette transporter gene, which functions to enable transport of iron from the mitochondria to the cytoplasm. Furthermore, ABCB7 gene silencing in HeLa cells causes an accumulation of iron in the mitochondria. We have studied the role of ABCB7 in RARS by DNA sequencing, methylation studies, and gene expression studies in primary CD34(+) cells and in cultured erythroblasts. The DNA sequence of the ABCB7 gene is normal in patients with RARS. We have investigated ABCB7 gene expression levels in the CD34(+) cells of 122 MDS cases, comprising 35 patients with refractory anemia (RA), 33 patients with RARS and 54 patients with RA with excess blasts (RAEB), and in the CD34(+) cells of 16 healthy controls. We found that the expression levels of ABCB7 are significantly lower in the RARS group. RARS is thus characterized by lower levels of ABCB7 gene expression in comparison to other MDS subtypes. Moreover, we find a strong relationship between increasing percentage of bone marrow ring sideroblasts and decreasing ABCB7 gene expression levels. Erythroblast cell cultures confirm the low levels of ABCB7 gene expression levels in RARS. These data provide an important link between inherited and acquired forms of sideroblastic anemia and indicate that ABCB7 is a strong candidate gene for RARS.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/fisiología , Anemia Refractaria/metabolismo , Anemia Sideroblástica/metabolismo , Antígenos CD34/biosíntesis , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Células Precursoras Eritroides/metabolismo , Perfilación de la Expresión Génica , Silenciador del Gen , Células HeLa , Humanos , Modelos Biológicos , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Secuencia de ADNRESUMEN
Circulating nucleic acids have been shown to have potential as non-invasive diagnostic markers in cancer. We therefore investigated whether microRNAs also have diagnostic utility by comparing levels of tumour-associated MIRN155 (miR-155), MIRN210 (miR-210) and MIRN21 (miR-21) in serum from diffuse large B-cell lymphoma (DLBCL) patients (n = 60) with healthy controls (n = 43). Levels were higher in patient than control sera (P = 0.009, 0.02 and 0.04 respectively). Moreover, high MIRN21 expression was associated with relapse-free survival (P = 0.05). This is the first description of circulating microRNAs and suggests that microRNAs have potential as non-invasive diagnostic markers for DLBCL and possibly other cancers.
Asunto(s)
Biomarcadores de Tumor/sangre , Linfoma de Células B Grandes Difuso/diagnóstico , MicroARNs/sangre , ARN Neoplásico/sangre , Adulto , Femenino , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
Coagulation factors are produced by the liver. It is well recognized that liver transplantation can cure haemophilia. We described a case of thrombophilia acquired due to liver transplantation from a donor with heritable thrombophilia.
Asunto(s)
Resistencia a la Proteína C Activada/etiología , Trasplante de Hígado/efectos adversos , Trombofilia/genética , Resistencia a la Proteína C Activada/diagnóstico , Factor V/genética , Humanos , Masculino , Persona de Mediana Edad , Trombosis de la Vena/etiologíaRESUMEN
The myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal disorders of the haematopoietic stem cell and primarily involve cells of the myeloid lineage. Using cDNA microarrays comprising 6000 human genes, we studied the gene expression profiles in the neutrophils of 21 MDS patients, seven of which had the 5q- syndrome, and two acute myeloid leukaemia (AML) patients when compared with the neutrophils from pooled healthy controls. Data analysis showed a high level of heterogeneity of gene expression between MDS patients, most probably reflecting the underlying karyotypic and genetic heterogeneity. Nevertheless, several genes were commonly up or down-regulated in MDS. The most up-regulated genes included RAB20, ARG1, ZNF183 and ACPL. The RAB20 gene is a member of the Ras gene superfamily and ARG1 promotes cellular proliferation. The most down-regulated genes include COX2, CD18, FOS and IL7R. COX2 is anti-apoptotic and promotes cell survival. Many genes were identified that are differentially expressed in the different MDS subtypes and AML. A subset of genes was able to discriminate patients with the 5q- syndrome from patients with refractory anaemia and a normal karyotype. The microarray expression results for several genes were confirmed by real-time quantitative polymerase chain reaction. The MDS-specific expression changes identified are likely to be biologically important in the pathophysiology of this disorder.
