PRPS1 and acute lymphoblastic leukemia: As shown in Figure 1A‐D, the viability of Reh cells harboring PRPS1 mutants dramatically increased after treatment with both 6‐MP and 6‐TG, whereas the cells harboring PRPS1 WT showed slight resistance to 6‐MP and 6‐TG, consistent with our previous findings that relapse‐specific PRPS1 mutations confer thiopurine resistance.5 Meanwhile, these cells had a minor resistance to doxorubicin (DXR) but no significant sensitivity to vincristine (VCR) (Figure 1E and F), both of drugs are also commonly used in ALL treatment.