Summary:
This logical network model integrate signalling, transcriptional and epigenetic regulatory mechanisms underlying the Acute Promyelocytic Leukaemia cell responses to RA treatment depending on their genetic background. The explicit inclusion of the histone methyltransferase EZH2 allowed us to assess its role in the maintenance of the resistant phenotype, distinguishing between its canonical and non-canonical activities. Ultimately, this model offers a solid basis to assess the roles of novel regulatory mechanisms, as well as to explore novel therapeutical approaches in silico.