Plasma Flt3-ligand (FL) concentration as a bio-indicator of radiation-induced bone marrow aplasia
Jean Marc Bertho, Johanna Frick, Christelle Demarquay, Alain Chapel, Dominique Thierry, Jocelyne Aigueperse
31st Annual Meeting of "International Society for experimental haematology" - Montreal, 5-9 juillet 2002
Bone marrow aplasia is one of the first consequence threatening victim’s life after an accidental irradiation. The choice between different treatments (e.g. transfusion, cytokine treatments or stem cell transplantation) is mainly based upon the estimation of the irradiation dose. However, this does not indicate the severity of the stroke to the bone marrow, especially with heterogeneous irradiation. Thus, it is of importance to get biological indicators, giving a precise picture of radiation damage to the bone marrow.
It was shown by others that plasma FL concentration in humans was inversely correlated to the number of CFC in the bone marrow. We thus hypothesise that plasma FL concentration could be used as a bio-indicator of bone marrow damage. In order to verify this hypothesis, a non-human primate model was used. The basal level of FL was first measured in healthy animals. We also verify that no variation of plasma FL level was observed according to the age or the sex of animals, or to the circadian rhythm.
In a first set of experiment, 7 animals were irradiated with doses ranging from 2 to 8 Gy. The follow up of plasma FL showed an increase in concentration as soon as day 3 post-irradiation. The increase in plasma FL concentration on day five post-irradiation was correlated to the dose of irradiation, but also to the duration and the severity of neutropenia and thrombocytopenia subsequently observed in these animals. The evolution of plasma FL level was inverted as compared to the evolution of blood cell counts, and sustained levels of plasma FL were observed until the return to normal blood cell counts.
When irradiated animals were treated with either bone marrow transplantation or hematopoietic acting cytokines, plasma FL level returned to normal values earlier than in non treated animals, in parallel to the earlier return to normal values of blood cell counts. Moreover, a inverse correlation between the number of CD34+ cells in the bone marrow and the plasma FL concentration was observed. These results show that plasma FL concentration is a bio-indicator of bone marrow function, predictive of the radiation-induced damage.