RESUMO
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.
Assuntos
Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas Inibidoras de Apoptose/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Células Sanguíneas/metabolismo , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Epitopos de Linfócito T/imunologia , Feminino , Proteínas de Fusão bcr-abl/genética , Expressão Gênica/genética , Humanos , Mesilato de Imatinib , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/imunologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Survivina , Resultado do Tratamento , Adulto JovemRESUMO
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.
