RESUMEN
OBJECTIVE: To investigate the exprassion of WT1 gene in patients with adult acute myeloid leukemia (AML) and its clinical significance. METHODS: Sixty-three newly diagnosed patients with acute myeloid leukemia were selected. Quantitative RT-PCR was used to detect the expression of WT1 gene in the 63 AML patients and 20 non-AML controls. RESULTS: WT1 gene was highly expressed in AML patents and its expression in the low-risk group was significantly lower than that in middle-risk group and high-risk group (P<0.05), and no significant difference of WT1 gene expression between middle-risk and high-risk group was observed. In the patients of middle-risk and high-risk patients, the expression of WT1 gene in the remission group was significantly lower than that in the patients of non-remission after treatment (P<0.05). The non-remission patients after first treatment in middle-risk and high-risk group were treated with second induction therapy. After second induction therapy, the WT1 expression in remission patients was significantly decreased (P<0.05) in comparison with that in patients still in non-remission. There was a negative correlation between WT1 expression and the 2-year overall survival rate in the newly diagnosed middle and high-risk AML patients. CONCLUSION: The detection of WT1 gene expression can help to divide AML patients into low-/middle-/high-risk groups and to evaluate therapeutic response and clinical prognosis in middle and high-risk AML patients.
Asunto(s)
Leucemia Mieloide Aguda , Enfermedad Aguda , Expresión Génica , Humanos , Neoplasia Residual , Pronóstico , Proteínas WT1RESUMEN
Aplastic anaemia (AA) is a life-threatening hematopoietic disorder characterized by hypoplasia and pancytopenia with increasing fat cells in the bone marrow (BM). The BM-derived mesenchymal stem cells (MSCs) from AA are more susceptible to be induced into adipogenic differentiation compared with that from control, which may be causatively associated with the fatty BM and defective hematopoiesis of AA. Here in this study, we first demonstrated that levamisole displayed a significant suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Mechanistic investigation revealed that levamisole could increase the expression of ZFP36L1 which was subsequently demonstrated to function as a negative regulator of adipogenic differentiation of AA BM-MSCs through lentivirus-mediated ZFP36L1 knock-down and overexpression assay. Peroxisome proliferator-activated receptor gamma coactivator 1 beta (PPARGC1B) whose 3'-untranslated region bears adenine-uridine-rich elements was verified as a direct downstream target of ZFP36L1, and knock-down of PPARGC1B impaired the adipogenesis of AA BM-MSCs. Collectively, our work demonstrated that ZFP36L1-mediated post-transcriptional control of PPARGC1B expression underlies the suppressive effect of levamisole on the adipogenic differentiation of AA BM-MSCs, which not only provides novel therapeutic targets for alleviating the BM fatty phenomenon of AA patients, but also lays the theoretical and experimental foundation for the clinical application of levamisole in AA therapy.
Asunto(s)
Adipocitos/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Anemia Aplásica/genética , Factor 1 de Respuesta al Butirato/genética , Proteínas Portadoras/genética , Levamisol/farmacología , Células Madre Mesenquimatosas/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Adipogénesis/genética , Adolescente , Adulto , Anemia Aplásica/metabolismo , Anemia Aplásica/patología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/patología , Factor 1 de Respuesta al Butirato/agonistas , Factor 1 de Respuesta al Butirato/metabolismo , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Diferenciación Celular , Femenino , Regulación de la Expresión Génica , Genes Reporteros , Humanos , Luciferasas/genética , Luciferasas/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Persona de Mediana Edad , Cultivo Primario de Células , Proteínas de Unión al ARN , Transducción de SeñalRESUMEN
A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13×10(9)/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections.
