title: Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene.
abstract: Acute lymphoblastic leukemia (ALL) is a major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients who experience severe adverse events. L-Asparaginase is an effective antineoplastic agent used in chemotherapy of ALL. Despite its indisputable indication, hypersensitivity reactions are common. In those cases, discontinuation of treatment is usually needed and anti-asparaginase antibody production may also attenuate asparaginase activity, compromising its antileukemic effect. Till now, six pharmacogenetic studies have been performed in order to elucidate possible genetic predisposition for inter-individual differences in asparaginase hypersensitivity. In this review we have summarized the results of those studies which describe the involvement of four different genes, being polymorphisms in the glutamate receptor, ionotropic, AMPA 1 (GRIA1) the most frequently associated with asparaginase hypersensitivity. We also point to new approaches focusing on epigenetics that could be interesting for consideration in the near future.
authors.forename: Maria
authors.initials: M
authors.lastname: Lopez-Santillan
authors.forename: Leire
authors.initials: L
authors.lastname: Iparraguirre
authors.forename: Idoia
authors.initials: I
authors.lastname: Martin-Guerrero
authors.forename: Angela
authors.initials: A
authors.lastname: Gutierrez-Camino
authors.forename: Africa
authors.initials: A
authors.lastname: Garcia-Orad
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D001215:Asparaginase / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001215:Asparaginase; D018091:Receptors, AMPA; D017470:Receptors, Glutamate