Here, we describe targeted sequencing of 538 cancer-relevant genes using a clinical sequencing platform in a set of 57 HD-ALL patients lacking the common KRAS and NRAS codon 12 and 13 hotspot mutations and common gene deletions, to enrich for discovery of novel driver genes and to assess recurrently-mutated pathways in HD-ALL tumorigenesis. This evidence concerns the gene KRAS and acute lymphoblastic leukemia.