Quantitative modeling of chronic myeloid leukemia: insights from radiobiology
Cet article passe en revue les travaux récents sur la modélisation mathématique de la dynamique cellulaire des leucémies myéloïdes chroniques et évalue leur pertinence à l'aune des recherches en radiobiologie
Mathematical models of chronic myeloid leukemia (CML) cell population dynamics are being developed to improve CML understanding and treatment. We review such models in light of relevant findings from radiobiology, emphasizing three points. First, the CML models almost all assert that the latency time, from CML initiation to diagnosis, is at most ~10 years. Meanwhile, current radiobiological estimates, based on Japanese atomic-bomb survivor data, indicate a substantially higher maximum, suggesting longer-term relapses and suggesting extra resistance mutations. Second, different CML models assume different numbers, between 400 and 106, of normal hematopoietic stem cells (HSC). Radiobiological estimates favor values > 106 for the number of normal cells (often assumed to be the HSC) that are at risk for a CML-initiating BCR-ABL translocation. Moreover there is some evidence for an HSC dead-band hypothesis, consistent with HSC numbers being very different across different healthy adults. Third, radiobiologists have found that sporadic (background, age-driven) chromosome translocation incidence increases with age during adulthood. BCR-ABL translocation incidence increasing with age would provide a hitherto under-analyzed contribution to observed background adult-onset CML incidence acceleration with age, and would cast some doubt on stage-number inferences from multi-stage carcinogenesis models in general.
Blood , résumé, 2012