Common themes in the pathogenesis of acute myeloid leukemia

The pathogenesis of acute myeloid leukemia is associated with the appearanc e of oncogenic fusion proteins generated as a consequence of specific chrom osome translocations. Of the two components of each fusion protein, one is generally a transcription factor, whereas the other partner is mo re variab le in function, but often involved in the control of cell survival and apop tosis. As a consequence, AML-associated fusion proteins function as aberran t transcriptional regulators that interfere with the process of myeloid dif ferentiation, determine a stage-specific arrest of maturation and enhance c ell survival in a cell-type specific manner. The abnormal regulation of tra nscriptional networks occurs through common mechanisms that include recruit ment of aberrant corepressor complexes, alterations in chromatin remodeling , and disruption of specific subnuclear compartments. The identification an d analysis of common and specific target genes regulated by AML fusion prot eins will be of fundamental importance for the full understanding of acute myeloid leukemogenesis and for the implementation of disease-specific drug design.