Hyper-radiosensitivity affects low-dose acute myeloid leukemia incidence in a mathematical model

• DOI: 10.1007/s00411-022-00981-7
• Publication Date: 2022-07-21T18:02:49Z
• Authors: Sjors Stouten; Ben Balkenende; Lars Roobol; Sjoerd Verduyn Lunel; Christophe Badie; Fieke Dekkers
• Keywords: Radiosensitivity; Myeloid leukaemia; Radiation Tolerance; Low Dose Radiation

Abstract In vitro experiments show that the cells possibly responsible for radiation-induced acute myeloid leukemia (rAML) exhibit low-dose hyper-radiosensitivity (HRS). these cells, HRS is excess cell killing at low doses. Besides endpoint of killing, has also been shown to stimulate formation chromosomal aberrations such as deletions. Although investigated extensively, little known about possible effect on cancer risk. CBA mice, rAML can largely be explained in terms a Sfpi1 deletion and point mutation remaining gene copy. The aim this paper present quantify mechanisms through which may influence incidence mice. To accomplish this, mechanistic mouse model was developed study HRS-dependent AML onset after photon irradiation. computed under assumptions target cells: (1) do not HRS; (2) only stimulates killing; or (3) deletion. absence (control), dose-response curve approximated with linear-quadratic function absorbed dose. Compared control, assumption lowered incidence, whereas increased observed doses if additionally induction conclusion, cellular affects number surviving pre-leukemic an which, depending assumption, directly translates lower/higher probability developing rAML. Low-dose affect risk general by altering certain mutations occur/persist.