Gabriel Querrec, François-Régis Bataille, Vincent Rodin,
Jean-François Abgrall and Jacques Tisseau.
Computer simulation of multiple myeloma in the context of systems biology.
In 10th International Myeloma workshop,
volume 90, supplement no 1 of Haematologica, the haematology journal,
pages 92-93, Sydney (Australia), 10-14 April 2005.
Abstract:
Cancer is complex adaptive system. We assume that multiple
myeloma (MM) can be studied in the context of complexity
using Systems Biology (SB). SB is a new field in biology
aimed at understanding biology at systems level. We
developed 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
signals. Moreover, CD45 expression is stimulated
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 loss
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 InVirtuo simulation enables simulation
of emergent behavior 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
allow research of new therapeutic targets and therapies.
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[Querrec05b.pdf]