Estimation of the target stem-cell population size in chronic myeloid leukemogenesis

Estimation of the number of hematopoietic stem cells capable of causing chr onic myeloid leukemia (CML) is relevant to the development of biologically based risk models of radiation-induced CML. Through a comparison of the age structure of CML incidence data from the Surveillance, Epidemiology, and E nd Results (SEER) Program and the age structure of chromosomal translocatio ns found in healthy subjects, the number of CML target stem cells is estima ted for individuals above 20 years of age. The estimation involves three st eps. First, CML incidence among adults is fit to an exponentially increasin g function of age. Next, assuming a relatively short waiting time distribut ion between BCR-ABL induction and the appearance of CML, an exponential age function with rate constants fixed to the values found for CML is fitted t o the translocation data. Finally, assuming that translocations are equally likely to occur between any two points in the genome, the parameter estima tes found in the first two steps are used to estimate the number of target stem cells for CML. The population-averaged estimates of this number are fo und to be 1.86x10(8) for men and 1.21x10(8) for women; the 95% confidence i ntervals of these estimates are (1.34x10(8), 2.50x10(8)) and (0.84x10(8), 1 .83x10(8)), respectively.