In summary, by targeted sequencing of cancer genes in ALL samples collected at diagnosis and relapse, we identified distinctive differences in the mutational landscape between the immunophenotypes and genetic subtypes of ALL, discovered ATRX as a novel putative driver gene in ALL and identified EP300, ARID1A and SH2B3 as relapse-associated genes. This evidence concerns the gene ARID1A and acute lymphoblastic leukemia.