Gabriel Querrec, François-Régis Bataille, Vincent Rodin,
Jean-François Abgrall and Jacques Tisseau.
Computer simulation of multiple myeloma in the context of systems biology.
Ecole thématique: Modélisation de systèmes biologiques
complexes dans le contexte de la génomique, page 159,
Montpellier (France), 4-8 Avril 2005.
Abstract:
Cancer is complex adaptive system. We assume that multiple
myeloma (MM) can be study in the context of complexity
using Systems Biology (SB). SB is a new field in biology
aims at understanding biology at systems level. We
develop the "In Virtuo" experimentation for SB using virtual
environment. Multiagent systems provide an attractive
computer framework for SB and "In Virtuo" approachs.
We implement a computer simulation supporting the maturation
model of myeloma cells based on the CD45 expression.
One has shown that CD45 expression decreases with the
maturation of the cells and CD45 annihilation is a critical
prognostic for patient survival. CD45 expression is also necessary
for IL6 proliferation signals but inhibits IGF-1 proliferation
signal. Moreover, CD45 expression is stimulate by IL6 and its
activity inhibited by dimerization. The kinetics of CD45 dimerization
depends of the molecule isoform.
So, we have developed a computer simulation based on a
multiagent system which integrates the model of myeloma
cell previously described in their micro-environnement.
The simulation shows that kinetics of MM tumor presents an
exponential shape which is characteristic of the
first stages of tumor growth. Next, we can observe the lost
of tumor connectivity, which was previously shown to
occur with tumor evolution. We assume that CD45 isoform
is an important feature for the proliferation signal choice (data not
shown).
Holistic study, by the way of "In Virtuo" simulation enables to simulate
emergent behaviour of MM. The simulation shows the importance
of the microenvironement and the CD45 isoform for tumor
evolution. Moreover, we assume that our original approach may
allows research of new therapeutic targets and therapies.
[Querrec05a.pdf]