title: Pharmacogenetic considerations for acute lymphoblastic leukemia therapies.
abstract: BACKGROUND
  Advances in our understanding of the pathobiology of childhood acute lymphoblastic leukemia (ALL) have led to risk-targeted treatment regimens and remarkable improvement in survival rates. Still, up to 20% of patients experience treatment failure due to drug resistance. Treatment-related toxicities are often life-threatening and are the primary cause of treatment interruption, while ALL survivors may develop complications due to exposure to chemotherapy and/or irradiation during a vulnerable period of development. Different factors may contribute to variable treatment outcomes including patient genetics that has been shown to play important role.
  
  
  METHODS
  This review summarizes candidate gene and genome-wide association studies that identified common polymorphisms underlying variability in treatment responses including a few studies addressing late effects of the treatment. Genetic variants influencing antileukemic drug effects or leukemic cell biology have been identified, including for example variants in folate-dependent enzymes, influx and efflux transporters, metabolizing enzymes, drug receptor or apoptotic proteins.
  
  
  CONCLUSIONS
  Many pharmacogenetic studies have been conducted in ALL and a variety of potential markers have been identified. Yet more comprehensive insight into genome variations influencing drug responses is needed. Whole exome/genome sequencing, careful study design, mechanistic explanation of association found and collaborative studies will ultimately lead to personalized treatment and improved therapeutic and health outcomes.
authors.affiliation: University Health Center Bordeaux, Heamatology Laboratory , Bordeaux , France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dulucq
authors.forename: Caroline
authors.initials: C
authors.lastname: Laverdière
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins