Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Femenino , Regulación Leucémica de la Expresión Génica , Estudios de Asociación Genética , Humanos , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
It has been demonstrated that aberrant expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. Recently, specific miRNAs may serve as potential biomarkers for the diagnosis and prognosis of various types of tumor. MiR-23a is known to play important role in the development of cancers and deregulated in various hematological malignancies. The aim of the present study is to explore miR-23a as potential diagnostic and/or prognostic marker of diffuse large B-cell lymphoma (DLBCL). We compared the expression level of miR-23a in DLBCL patients (n = 104) and reactive lymph nodes as controls (n = 28) from formalin-fixed, paraffin-embedded tissues using quantitative reverse transcription-polymerase chain reaction. The expression level of miR-23a was significantly higher in DLBCL patients than in controls (P = 0.001). No significant association was observed between the miR-23a expression level and clinical features such as age, gender, Ann Arbor stage, performance status, lactate dehydrogenase, extranodal sites and International Prognostic Index score (IPI). Kaplan-Meier analysis showed that higher expression level of miR-23a was significantly associated with a poor overall survival (OS) in DLBCL patients (log-rank test, P = 0.029), and multivariable Cox regression revealed the expression of miR-23a (adjusted P = 0.034) and IPI (adjusted P = 0.021) was independently associated with OS. To our knowledge, we provide here the first evidence that miR-23a may represent a diagnostic and prognostic marker for DLBCL. DLBCL patients with a high expression level of miR-23a had a shorter OS than patients with a lower expression level. Further investigation of the changes may be of prognostic significance in clinical practice.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/mortalidad , MicroARNs/genética , MicroARNs/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Sensibilidad y Especificidad , Resultado del Tratamiento , Adulto JovenRESUMEN
The aim of this study was to investigate whether polymorphisms of - 938C/A and Thr43Ala in the BCL-2 gene and G - 248A in the BAX gene are associated with the risk of developing non-Hodgkin lymphoma (NHL). We genotyped polymorphisms of - 938C/A and Thr43Ala in the BCL-2 gene and G-248A in the BAX gene among 424 patients with NHL and 446 controls. We found that the - 938AA genotype of the BCL2 gene was significantly associated with the risk of developing NHL (p < 0.001) and this genotype was associated with advanced stage (p = 0.01). Meanwhile, individuals having - 248AG + AA genotypes were significantly associated with an increased risk of NHL (p = 0.01), and these genotypes were associated with larger tumor size (p = 0.02). The present study demonstrated that the - 938AA genotype of the BCL-2 gene and - 248AG + AA genotype of the BAX gene may be susceptible genotypes for NHL. There appeared to be an impact of the BCL2 - 938AA genotype on advanced stage and - 248AG + AA genotypes on tumor size in NHL.
Asunto(s)
Transformación Celular Neoplásica/genética , Linfoma no Hodgkin/genética , Polimorfismo Genético , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteína X Asociada a bcl-2/genética , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Linfoma no Hodgkin/diagnóstico , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Polimorfismo de Nucleótido Simple , Riesgo , Factores de Riesgo , Carga TumoralRESUMEN
This study was aimed to overexpress gene hßc in NB4 cells via the method of lentivirus-mediated gene transfer, to observe the differentiation behaviour change of hßc over-expressing NB4 cells treated with IL-3 or GM-CSF, to explore the relationship between hßc gene and the differentiation behaviour of NB4 cells. The targeted hßc gene was amplified by PCR from the cloned vector carrying ORF of hßc. The PCR product containing PmeI and BstBI site introduced by primer was digested, and then cloned into lentivirus vector pRRLSIN.cPPT.PGK/IRES/GFP.WPRE to construct a lentiviral vector carrying hßc, named pLV-hßc. And the pLV-hßc plasmid was confirmed by restriction and sequencing. The recombinant lentivirus was produced by co-transfecting three plasmids into 293T packing cells. After transfection, the lentiviral supernatant was collected to transfect NB4 cells. GFP expression was examined by fluorescent microscope and the expression of hßc gene was detected by Western blot. Then, the NB4 cells over-expressing hßc were treated with IL-3 (10 ng/ml), GM-CSF (10 ng/ml), ATRA (1 µmol/L) respectively, and the CD11b expression, morphology and differentiation behaviour changes of every groups were observed by flow cytometry and microscopy, while NB4 cells transfected with blank lentivirus (NB4-blank cells) were used as controls. The results showed that the recombinant lentivirus vector carrying hßc gene could efficiently transfect NB4 cells and made NB4 cells to stably over-express hßc gene. The expression of CD11b was up-regulated in NB4-hßc cells treated with of IL-3 or GM-CSF, but it was not as obvious as the effect of ATRA, and no morphological change was observed in NB4 hßc cells treated with the IL-3 or GM-CSF. It is concluded that IL-3 or GM-CSF can induce NB4 cells over-expressing hßc to differentiate to neutrophils, but can not make them fully matured.