Common themes in the pathogenesis of acute myeloid leukemia

Myriam Alcalay, Annette Orleth, Carla Sebastiani, Natalia Meani, Ferdinando Chiaradonna, Cristina Casciari, Maria Teresa Sciurpi, Vania Gelmetti, Daniela Riganelli, Saverio Minucci, Marta Fagioli, Pier Giuseppe Pelicci

Research output: Contribution to journalArticlepeer-review

Abstract

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 corepressor 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.

Original languageEnglish
Pages (from-to)5680-5694
Number of pages15
JournalOncogene
Volume20
Issue number40 REV. ISS. 4
DOIs
Publication statusPublished - Sep 10 2001

Keywords

  • Acute myeloid leukemia
  • Cell survival
  • Differentiation
  • Fusion proteins
  • Transcription factors

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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