Mutations that affect GR residue R477 were also described in patients with primary cortisol resistance58 and GC-resistant ALL cell lines.59 Of note, depending on the type of amino acid substitution, the R477 mutant can either act as dominant negative or not.51 Also, de novo NR3C1 deletions were identified in 28% (4/14),28 10% (5/51),29 or 16% (5/31)30 of relapsed childhood ETV6/RUNX1 ALL, which were associated with poor response to GC treatment. This evidence concerns the gene NR3C1 and acute lymphoblastic leukemia.