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Título : A closer look at specific therapeutic strategies in leukemia
Creador: Martinez Mancilla M.
Nivel de acceso: Open access
Palabras clave : Antineoplásicos - uso terapéutico
Ensamble y Desensamble de Cromatina
Inhibidores Enzimáticos - uso terapéutico
Humanos
Leucemia - metabolismo
Leucemia - terapia
Transducción de Señales
Antineoplastic Agents - therapeutic use
Chromatin Assembly and Disassembly
Enzyme Inhibitors - therapeutic use
Humans
Leukemia - metabolism
Leukemia - therapy
Signal Transduction
Acute leukemia; HDAC; Specific targeted therapy
Descripción : Leukemia-associated fusion genes are detected in a significant proportion of newly diagnosed cases, where genes encoding transcription factors are usually found at one of the breakpoints. Activated fusion proteins, such as PML-RARα and AMLI-ETO, have been shown to inhibit cellular differentiation by recruitment of nuclear corepressor complexes, which maintain local histone deacetylase (HDAC) in a variety of hematologic lineage-specific gene promoters. This HDAC-dependent transcriptional repression appears as a common pathway in the development of leukemia and could represent an important target for new therapeutic agents. On the other hand, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways involved normally in both apoptosis and proliferation. This aberrant activity is affected by signal transduction inhibitors (STIs), which block or prevent the oncogenic pathway. In this review, we present a closer took at our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction. In addition, the application of low molecular weight drugs for human leukemia treatment based in this knowledge results in durable clinical remission and acceptable risk of toxic effects that should increase the cure rate. We hope that this review will provide timely information to the readers. © 2004 Taylor & Francis Ltd.
Colaborador(es) u otros Autores: Zafra G.
Reynoso-Gómez E.
Martinez-Avalos A.
Rivera-Luna R.
Gariglio P.
Fecha de publicación : 2004
Tipo de publicación: Revisión
Formato: pdf
Identificador del Recurso : 10.1080/10428190410001683741
Fuente: Leukemia and Lymphoma 45(9):1767 - 1773
URI : http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/1803
Idioma: eng
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