HLA-DRB1*07:01 is associated with a higher risk of asparaginase allergies.

ABSTRACT: Asparaginase is a therapeutic enzyme used to treat leukemia and lymphoma, with immune responses resulting in suboptimal drug exposure and a greater risk of relapse. To elucidate whether there is a genetic component to the mechanism of asparaginase-induced immune responses, we imputed human leukocyte antigen (HLA) alleles in patients of European ancestry enrolled on leukemia trials at St. Jude Children's Research Hospital (n = 541) and the Children's Oncology Group (n = 1329). We identified a higher incidence of hypersensitivity and anti-asparaginase antibodies in patients with HLA-DRB1*07:01 alleles (P = 7.5 × 10(-5), odds ratio [OR] = 1.64; P = 1.4 × 10(-5), OR = 2.92, respectively). Structural analysis revealed that high-risk amino acids were located within the binding pocket of the HLA

SUBMITTER: Fernandez CA 

PROVIDER: S-EPMC4141516 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature