Preliminary Acute Promyelocytic Leukemia (APL) whole exome sequencing (WES) studies have identified a huge number of somatic mutations affecting more than a hundred different genes mainly in a non-recurrent manner, suggesting that APL is a heterogeneous disease with secondary relevant changes not yet defined.. The mutational landscape of Acute Promyelocytic Leukemia reveals an interacting network of co-occurrences and recurrent mutations

To extend our knowledge of subtle genetic alterations involved in APL that might cooperate with PML/RARA in the leukemogenic process, we performed a comprehensive analysis of somatic mutations in APL combining WES with sequencing of a custom panel of targeted genes by next-generation sequencing. To select a reduced subset of highly confidence candidate driver genes further in silico analysis were carried out. After prioritization and network analysis we found recurrent deleterious mutations in 10 individual genes with a strong potential of being involved in APL pathogenesis. Our network analysis of multiple mutations provides a reliable approach to prioritize genes for additional analysis, improving our knowledge of the leukemogenesis interactome. Additionally, we have defined a functional module in the interactome of APL, hypothesizing that might be not as important the number or the specific combinations of mutations harbored in each patient as the perturbation caused in biological key functions triggered by several not necessarily recurrent mutations.