RESUMEN
Tyrosine-kinase inhibitors are very effective in patients with CML, but in most cases the disease relapses after their discontinuation. As a result, novel approaches should be considered, such as anti-survivin treatment or anti-survivin-based immunotherapy. To gain insight into the roles of survivin isoform expression and specific CD8(+) T cells in CML, we investigated 51 patients at different stages, both at diagnosis and during treatment. We demonstrated that (i) patients at advanced-stage displayed an increased expression of the standard-survivin form along with a significant decrease of survivin-2B and -ΔEx3 levels, (ii) patients in chronic phase with higher expression of the standard-survivin exhibited a 3.5-fold increased probability not to achieve an optimal response to imatinib (p=0.048), (iii) responders displayed a significant up-regulation of all survivin isoforms in bone marrow, and (iv) anti-survivin CD8(+) T cells were undetectable both at diagnosis and during treatment. Accordingly, our results question the validity of immunotherapeutic approaches targeting survivin in CML.
Asunto(s)
Progresión de la Enfermedad , Resistencia a Antineoplásicos/fisiología , Proteínas Inhibidoras de la Apoptosis/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Linfocitos T Citotóxicos/inmunología , Adulto , Anciano , Antineoplásicos/uso terapéutico , Benzamidas , Células Sanguíneas/metabolismo , Células de la Médula Ósea/inmunología , Células de la Médula Ósea/metabolismo , Epítopos de Linfocito T/inmunología , Femenino , Proteínas de Fusión bcr-abl/genética , Expresión Génica/genética , Humanos , Mesilato de Imatinib , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/inmunología , Isoformas de Proteínas/genética , Isoformas de Proteínas/inmunología , Isoformas de Proteínas/metabolismo , Survivin , Resultado del Tratamiento , Adulto JovenRESUMEN
We report a fatal case of a rhino-cerebral zygomycosis, caused by Rhizopus arrhizus (oryzae). The patient was suffering from idiopathic thrombopenic purpura, diagnosed 1 year earlier. He was already treated with methylprednisolone 5 months prior to his admission to the hospital for a loss of vision and pain in the left eye as well as left orbital cellulitis. After an initial empirical treatment with broad spectrum antibiotics and voriconazole (infection of unknown origin), the patient was treated with liposomal amphotericin as soon as a positive fungal culture revealed a zygomycete. Unfortunately, the mould was resistant to amphotericin B (MIC: 16 microg ml(-1)) and probably to posaconazole (MIC: 4 microg ml(-1)), which was co-administrated a few days later.