Section: New Results

Mathematical Modelling of Acute Myeloid Leukemia

Participants : Catherine Bonnet, Jean Clairambault [MAMBA project-team] , François Delhommeau [INSERM Paris (Team18 of UMR 872) Cordeliers Research Centre and St. Antoine Hospital, Paris] , Walid Djema, Emilia Fridman [Tel-Aviv University] , Pierre Hirsch [INSERM Paris (Team18 of UMR 872) Cordeliers Research Centre and St. Antoine Hospital, Paris] , Frédéric Mazenc, Hitay Özbay [Bilkent University] .

Our project is about the modeling and analysis of healthy and unhealthy cell population dynamics, with a particular focus on hematopoiesis, which is the process of blood cell production and continuous replenishment. We point out that medical research is now looking for new combined targeted therapies able to overcome the challenge of cancer cells (e.g. to stop overproliferation, to restore normal apoptosis rates and differentiation of immature cells, and to avoid the high toxicity effects that characterize heavy non-selective chemotherapy). In that quest, the ultimate goal behind mathematical studies is to provide some inputs that should help biologists to suggest and test new treatment, and to contribute within multi-disciplinary groups in the opening of new perspectives against cancer. Thus, our research project is imbued within a similar spirit and fits the expectations of a better understanding of the behavior of healthy and unhealthy blood cell dynamics. It involve intensive collaboration with hematologists from Saint Antoine hospital in Paris, and aims to analyze the cell fate evolution in treated or untreated leukemia, allowing for the suggestion of new anti-leukemic combined chemotherapy.

Cells have amazing features that allow them to guide their development paths and determine their individual and collective fates. Dedifferentiation and transdifferentiation (cell plasticity) are little understood phenomena that allow cells to regress from an advanced differentiated state to a less differentiated one, including the case where cells lose their specific function and become stem cells.

We have introduced cell plasticity into a class of mathematical models we are interested in. We explored a new model involving a dedifferentiation function in the case of two cell maturity stages (stem cells and progeny). We have highlighted the role that dedifferentiation may have in the survival of cancer cells during therapy. The latter hypothesis appears to be in line with some medical observations [48].

We have also developed and analyzed a model taking into the account the fact that few cells of the proliferating compartment may be arrested during an unlimited time [49].