Our previous studies demonstrated that RAS pathway mutations can drive relapse and generate a more chemo-resistant phenotype, supported by the enrichment of KRAS mutant cells during induction chemotherapy and the observation of RAS gene mutations consistently in the major clone at relapse.8 In this study, NRAS p.G12D and PTPN11 p.R351Q were detected in one iAMP21-ALL relapse sample as heterozygous variants (48% VAF). This evidence concerns the gene PTPN11 and acute lymphoblastic leukemia.