NT5C2 relapse-associated mutations. (A) NT5C2 relapse-associated mutations in B-cell ALL, T-cell ALL, and acute promyelocytic leukemia (APL). (B) Schematic representation of NT5C2 regulation. NT5C2 dimer protein is depicted with the arm region shown in pink, C terminus in royal blue, N terminus in orange, and helix A in purple. The arm region shown in gray represents a prediction based on modeling. Class I NT5C2 mutants lock the protein in an active helix A configuration. Class II NT5C2 mutants disrupt a switch-off mechanism mediated by the arm and intermonomeric pocket regions. The class III NT5C2 mutant protein lacks the C-terminus stabilizing element, leaving the protein in a more open configuration.