In recent years, various NGS studies of childhood and adult B-ALL and T-ALL have revealed a spectrum of somatic mutations in several genes involved in multiple canonical and non-canonical signaling pathways of ALL, such us transcriptional regulation, lymphoid differentiation and development, TP53 and the cell cycle, RAS signaling, JAK/STAT, NOTCH, PI3K/AKT/mTOR, Wnt/β-catenin signaling, chromatin structure modifiers, and epigenetic regulators. This evidence concerns the gene PIK3CA and acute lymphoblastic leukemia.