Pathogenic somatic variants in leukemia blasts from patients with early ALL relapse and associated with resistance to TPs have also been identified in 5′-nucleotidase, cytosolic II (encoded by NT5C2), which inactivates TIMPs and TGMPs; phosphoribosyl pyrophosphate synthetase 1 (PRPS1), which inhibits the anabolic enzyme HPRT1; and MSH6, which influences DNA mismatch repair (14–17). Here, PRPS1 is linked to leukemia.