Modeling low-dose radiation-induced acute myeloid leukemia in male CBA/H mice

Sjors Stouten*, Sjoerd Verduyn Lunel, Rosemary Finnon, Christophe Badie, Fieke Dekkers

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The effect of low-dose ionizing radiation exposure on leukemia incidence remains poorly understood. Possible dose-response curves for various forms of leukemia are largely based on cohorts of atomic bomb survivors. Animal studies can contribute to an improved understanding of radiation-induced acute myeloid leukemia (rAML) in humans. In male CBA/H mice, incidence of rAML can be described by a two-hit model involving a radiation-induced deletion with Sfpi1 gene copy loss and a point mutation in the remaining Sfpi1 allele. In the present study (historical) mouse data were used and these processes were translated into a mathematical model to study photon-induced low-dose AML incidence in male CBA/H mice following acute exposure. Numerical model solutions for low-dose rAML incidence and diagnosis times could respectively be approximated with a model linear-quadratic in radiation dose and a normal cumulative distribution function. Interestingly, the low-dose incidence was found to be proportional to the modeled number of cells carrying the Sfpi1 deletion present per mouse following exposure. After making only model-derived high-dose rAML estimates available to extrapolate from, the linear-quadratic model could be used to approximate low-dose rAML incidence calculated with our mouse model. The accuracy in estimating low-dose rAML incidence when extrapolating from a linear model using a low-dose effectiveness factor was found to depend on whether a data transformation was used in the curve fitting procedure.

Original languageEnglish
Pages (from-to)49-60
Number of pages12
JournalRadiation and Environmental Biophysics
Issue number1
Publication statusPublished - Mar 2021

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Copyright 2021 Elsevier B.V., All rights reserved.


  • Acute myeloid leukemia
  • CBA mice
  • Ionizing radiation exposure
  • LDEF
  • Low-dose
  • Mathematical modeling


Dive into the research topics of 'Modeling low-dose radiation-induced acute myeloid leukemia in male CBA/H mice'. Together they form a unique fingerprint.

Cite this