PhD student in Pharmacology
Université de Montréal, CHU Sainte-Justine
Award-winning publication: Ionizing radiation-induced expression of INK4a/ARF in murine bone marrow-derived stromal cell populations interferes with bone marrow homeostasis
Published in: Blood, 119(3), pages 717-726
"Various stimuli such as aging are proven to alter the bone marrow microenvironment, but it is unclear whether they also induce the senescence of stromal cells. Our study shows that ionizing radiation triggers the expression of senescence markers in murine bone marrow stromal cells. The results demonstrate the distinct sensitivities of bone marrow stromal cell populations and provide evidence that residual long-term damage to the microenvironment will alter B lymphopoiesis in an Ink4a/arf-dependant manner."
Ionizing radiation is used in hematopoietic transplant conditioning regimens to eliminate cancer cells and "make room" for healthy transplant cells. Cynthia Carbonneau observed that the absolute number of bone marrow hematopoietic cells is lower in irradiated mice than in control mice—a finding in keeping with Collis et al. (Radiation Research, 2004). She also showed that ionizing radiation alters the bone marrow microenvironment, leading to the long-term deficiency of B lymphopoiesis, and thus fails to fulfill one of the two functions for which it is administered. In fact, the radiation brings about persistent side effects that are deleterious to the health of patients. Thankfully, there are drug entities (e.g. alkylating agents) that are effective against cancer cells and which are already in use in clinical settings. It is therefore foreseeable that radiation treatment will stop in the short to medium term.