The incidence of hematologic tumours: A cellular model for the age dependence

Most hematologic tumors (acute and chronic myelogenous leukemia, chronic lymphatic leukemia, polycythemia vera, and multiple myeloma) exhibit an exponential increase in incidence with advancing age of the host. This age-incidence pattern resembles that for carcinomas and can be explained by the accumulation of harmful mutations in the stem cells of the tissues of tumor origin during the course of normal aging. The age-incidence pattern for acute lymphatic leukemia is unique and complex with a linear increase in incidence from birth to age 3, an exponential decline in incidence form age 3 to 34, a low and constant rate of incidence from age 34 to 60, and a slight increase in incidence at ages greater than 60. We conclude that variation in tumor incidence with host age is determined by the pattern of cell proliferation in the tissue of tumor origin. We suggest that cell proliferation in the tissue of origin of acute lymphatic leukemia occurs in stages: (1) rapid stem cell proliferation from before birth to age 3, (2) random stem cell differentiation from age 3 to 34, and (3) a constant rate of stem cell proliferation and differentiation after age 34.