Subtype-specific regulatory network rewiring in acute myeloid leukemia
Menée sur des lignées cellulaires de leucémie myéloïde aiguë, cette étude met en évidence des mécanismes par lesquels, en fonction de mutations des gènes codant pour des facteurs de transcription (RUNX1, CEBPalpha), des molécules de signalisation (FTL3-ITD, RAS) et une protéine nucléaire (NPM1), un réseau de signalisation spécifique favorise la prolifération des cellules leucémiques
Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of alterations in transcription factors, epigenetic regulators and signaling molecules. To determine how different mutant regulators establish AML subtype–specific transcriptional networks, we performed a comprehensive global analysis of cis-regulatory element activity and interaction, transcription factor occupancy and gene expression patterns in purified leukemic blast cells. Here, we focused on specific subgroups of subjects carrying mutations in genes encoding transcription factors (RUNX1, CEBPα), signaling molecules (FTL3-ITD, RAS) and the nuclear protein NPM1). Integrated analysis of these data demonstrates that each mutant regulator establishes a specific transcriptional and signaling network unrelated to that seen in normal cells, sustaining the expression of unique sets of genes required for AML growth and maintenance.