Recently, next‐generation sequencing analyses of relapsed childhood ALL samples revealed somatic mutations in critical genes for drug metabolism, suggesting mechanisms for acquired drug‐resistant phenotypes; mutations in NT5C231, 32, 33 and PRPS1 genes 34 have been reported to be involved in the specific resistance to 6‐mercaptopurine in relapsed ALL. This evidence concerns the gene PRPS1 and acute lymphoblastic leukemia.