Chemotherapy-resistance mutations in relapsed ALL. (A) Most of the NT5C2 mutations identified in relapsed ALL are subclonal, identified in relatively few leukemic cells. In subsequent relapses, the subclonal NT5C2-mutated cells often disappeared or were diminished. (B) ALL relapse is frequently associated with different somatic mutations that confer thiopurine resistance, such as mutations in NT5C2 or PRPS1/2, which are involved in thiopurine metabolism, or mutations in MSH6/2, which induce thiopurine resistance via impaired DNA mismatch repair. 6-MP, 6-mercaptopurine.