title: The incidence of acute promyelocytic leukemia appears constant over most of a human lifespan, implying only one rate limiting mutation.
abstract: It is believed that most malignancies become more common with increasing age due to the requirement for several mutations to accumulate and subsequently interact. The age specific incidence of acute promyelocytic leukemia (APL) was investigated using population-based data from 77 million subject years of observation, yielding 149 consecutive cases. The incidence appears approximately constant with respect to age, an observation not previously reported with any other malignancy. These findings are most easily explained by there being only one rate limiting genetic event required to initiate the disease, although other, non-rate limiting mutations may also be necessary for disease development. It is also argued that this mutation is probably restricted to cells committed to differentiation, which may explain why APL is curable by chemotherapy.
authors.affiliation: Department of Haematology, Medicine and Therapeutics, Aberdeen, Foresterhill, UK.
authors.forename: M
authors.initials: M
authors.lastname: Vickers
authors.forename: G
authors.initials: G
authors.lastname: Jackson
authors.forename: P
authors.initials: P
authors.lastname: Taylor
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D006801:Humans; D015994:Incidence; D015473:Leukemia, Promyelocytic, Acute / Q000453:epidemiology* / Q000235:genetics; D008875:Middle Aged; D016296:Mutagenesis; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D014178:Translocation, Genetic; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein