The pathogenesis of acute myeloid leukemia is associated with the appearance of oncogenic fusion proteins generated as a consequence of specific chromosome translocations. Of the two components of each fusion protein, one is generally a transcription factor, whereas the other partner is more variable in function, but often involved in the control of cell survival and apoptosis. As a consequence, AML-associated fusion proteins function as aberrant transcriptional regulators that interfere with the process of myeloid differentiation, determine a stage-specific arrest of maturation and enhance cell survival in a cell-type specific manner. The abnormal regulation of transcriptional networks occurs through common mechanisms that include recruitment of aberrant co-repressor complexes, alterations in chromatin remodeling, and disruption of specific subnuclear compartments. The identification and analysis of common and specific target genes regulated by AML fusion proteins will be of fundamental importance for the full understanding of acute myeloid leukemogenesis and for the implementation of disease-specific drug design.
Common themes in the pathogenesis of acute myeloid leukemia / M. Alcalay, A. Orleth, C. Sebastiani, N. Meani, F. Chiaradonna, C. Casciari, M. T. Sciurpi, V. Gelmetti, D. Riganelli, S. Minucci, M. Fagioli, P. G. Pelicci. - In: ONCOGENE. - ISSN 0950-9232. - 20:40(2001 Sep 10), pp. 5680-94-5694.
|Titolo:||Common themes in the pathogenesis of acute myeloid leukemia|
|Parole Chiave:||Homozygote; DNA-Binding Proteins; Humans; Cell Differentiation; Transcription, Genetic; Leukemia, Myeloid, Acute; Hematopoiesis; Models, Biological; Translocation, Genetic; Cell Survival; Gene Expression Regulation, Neoplastic; Proto-Oncogene Proteins; Transcription Factors; Core Binding Factor Alpha 2 Subunit; Signal Transduction; Oncogene Proteins, Fusion|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||10-set-2001|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/sj.onc.1204642|
|Appare nelle tipologie:||01 - Articolo su periodico|