title: Pharmacogenetics of alkylator-associated acute myeloid leukemia.
abstract: Therapy-related acute myeloid leukemia (t-AML) is a lethal late complication of alkylator chemotherapy. The genetic basis of susceptibility to t-AML is poorly understood. Both t-AML and de novo AML are complex genetic diseases, requiring cooperating mutations in interacting pathways for disease initiation and progression. Germline variants of these 'leukemia pathway' genes may cooperate with somatic mutations to induce both de novo and therapy-related AML. Several cancer susceptibility syndromes have been identified that cause an inherited predisposition to de novo and t-AML. The genes responsible for these syndromes are also somatically mutated in sporadic AML. We reason that germline polymorphism in any gene somatically mutated in AML could contribute to t-AML risk in the general population. Identification of these susceptibility alleles should help clinicians develop tailored therapies that reduce the relative risk of t-AML.
authors.affiliation: Washington University School of Medicine, Division of Oncology, Stem Cell Biology Section, Campus Box 8007, 660 South Euclid Avenue, St Louis, MO 63110, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Knoche
authors.forename: Howard L
authors.initials: HL
authors.lastname: McLeod
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Graubert
mesh_terms: D000477:Alkylating Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods
chemical_list: D000477:Alkylating Agents