PIK3CA and acute lymphoblastic leukemia: We and others have shown that KMT2A-r infant ALL has few somatic mutations present in most leukemia cells, with an average of only 1.3 nonsilent mutations.5,6 Despite the paucity of major clonal mutations, activating kinase-PI3K/RAS mutations were present in approximately 50%, and may confer a poorer prognosis.5,7 About half of the activating mutations identified were subclonal with variant allele frequencies (VAFs) < 0.30 and some patients harbored several activating mutations at varying VAFs, suggesting multiple clones.