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. Leukemia (2000) 14, 722-726.

Age-specific incidence rates for cytogenetically-defined subtypes of acute myeloid leukaemia

“…A recent study which showed that the incidence rate of acute promyelocytic leukaemia (which is synonymous with t(15;17)) is constant with age supports these findings (Vickers et al, 2000). It is generally assumed that cancer incidence increases with age because of the time required to accumulate the requisite number of mutations to effect malignant transformation.…”

RARα-PLZF oncogene inhibits C/EBPα function in myeloid cells

“…Thus, in PLZF-RARα transgenic mice, loss of wild-type Plzf was sufficient to modify a CML-like disease into APL (12), in lieu of the coexpression of RARα-PLZF. The extensive network of protein-protein interaction entertained by both fusion proteins and the functional contribution of these fusion proteins to cell transformation could explain the fact that the incidence of APL does not increase with age, consistent with one or a limited number of rate-limiting mutation(s) (1,35). Fig.…”

“…Coimmunoprecipitations were performed using either in vitro translated 35 S radiolabeled protein, nuclear extracts, or cellular extracts from formaldehyde fixed cells as previously described (38). Individually synthesized proteins were preincubated for 30 min at 37°C to allow for protein-protein interactions to occur.…”

Population-based demographic study of karyotypes in 1709 patients with adult Acute Myeloid Leukemia

“…9 Favourable cytogenetic abnormalities, t(15;17), t(8;21) and inv(16) are known to occur more frequently in younger patients, 9,14,15 with a relatively constant incidence throughout life. 15,16 For each of these balanced translocation groups, a much larger proportion of patients are in the younger age decades, giving a more even age-related incidence, in contrast to the greater weighting towards the oldest age decades seen in trisomic and deletional abnormalities. Furthermore, t(15;17), t(9;11) and inv(16) represent a significantly younger subset in our dataset.…”