title: [Molecular hemato-oncology and new specific treatment strategies for leukemia].
abstract: 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-Raralpha 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 constitute an important target for new therapeutic agents. Alternatively, the Bcr-Abl oncoprotein shows high tyrosine kinase activity and deregulates signal transduction pathways normally involved 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 shed some light on our understanding of both the reversible transcriptional repression controlled by HDAC and the deregulated Bcr-Abl signal transduction pathway. In addition, the administration of low molecular weight drugs for human leukemia treatment based on this knowledge brings about a significant long-term clinical remission and an acceptable risk of toxic effects that should increase the cure rate.
authors.affiliation: Departamento de Genética y Biología Molecular, CINVESTA V-IPN, Mexico DF, Mexico.
authors.forename: Manuel
authors.initials: M
authors.lastname: Martínez-Mancilla
authors.forename: Gildardo
authors.initials: G
authors.lastname: Zafra-de la Rosa
authors.forename: Eduardo
authors.initials: E
authors.lastname: Reynoso-Gómez
authors.forename: Horacio
authors.initials: H
authors.lastname: Astudillo-de la Vega
authors.forename: María de Jesús
authors.initials: Mde J
authors.lastname: Nambo-Lucio
authors.forename: Luis
authors.initials: L
authors.lastname: Benítez-Bribiesca
authors.forename: Armando
authors.initials: A
authors.lastname: Martínez-Avalos
authors.forename: Roberto
authors.initials: R
authors.lastname: Rivera-Luna
authors.forename: Patricio
authors.initials: P
authors.lastname: Gariglio
mesh_terms: D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D006405:Hematology; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000235:genetics*; D008495:Medical Oncology; D008967:Molecular Biology
chemical_list: D006655:Histone Deacetylases