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Computation 2017, 5(1), 16; doi:10.3390/computation5010016

A Hybrid Computation Model to Describe the Progression of Multiple Myeloma and Its Intra-Clonal Heterogeneity

1
Institut Camille Jordan, UMR 5208 CNRS, University Lyon 1, Villeurbanne 69622, France
2
Laboratoire de Biométrie et Biologie Evolutive, UMR 5558 CNRS, University Lyon 1, Villeurbanne 69622, France
3
Mohammadia School of Engineering, Université Mohamed V, Rabat 10080, Morocco
4
Vanderbilt University Medical Center, Nashville, TN 37232-6307, USA
5
Institute of Numerical Mathematics, Russian Academy of Sciences, Moscow 119333, Russia
6
INRIA Team Dracula, INRIA Lyon La Doua, Villeurbanne 60603, France
*
Author to whom correspondence should be addressed.
Academic Editor: Rainer Breitling
Received: 18 October 2016 / Accepted: 5 March 2017 / Published: 10 March 2017
(This article belongs to the Special Issue Multiscale and Hybrid Modeling of the Living Systems)
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Abstract

Multiplemyeloma(MM)isageneticallycomplexhematologicalcancerthatischaracterized by proliferation of malignant plasma cells in the bone marrow. MM evolves from the clonal premalignant disorder monoclonal gammopathy of unknown significance (MGUS) by sequential genetic changes involving many different genes, resulting in dysregulated growth of multiple clones of plasma cells. The migration, survival, and proliferation of these clones require the direct and indirect interactions with the non-hematopoietic cells of the bone marrow. We develop a hybrid discrete-continuous model of MM development from the MGUS stage. The discrete aspect of the modelisobservedatthecellularlevel: cellsarerepresentedasindividualobjectswhichmove,interact, divide, and die by apoptosis. Each of these actions is regulated by intracellular and extracellular processes as described by continuous models. The hybrid model consists of the following submodels that have been simplified from the much more complex state of evolving MM: cell motion due to chemotaxis, intracellular regulation of plasma cells, extracellular regulation in the bone marrow, and acquisition of mutations upon cell division. By extending a previous, simpler model in which the extracellular matrix was considered to be uniformly distributed, the new hybrid model provides a more accurate description in which cytokines are produced by the marrow microenvironment and consumed by the myeloma cells. The complex multiple genetic changes in MM cells and the numerous cell-cell and cytokine-mediated interactions between myeloma cells and their marrow microenviroment are simplified in the model such that four related but evolving MM clones can be studied as they compete for dominance in the setting of intraclonal heterogeneity. View Full-Text
Keywords: multiple myeloma; intra-clonal heterogeneity; hybrid model multiple myeloma; intra-clonal heterogeneity; hybrid model
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Bouchnita, A.; Belmaati, F.-E.; Aboulaich, R.; Koury, M.J.; Volpert, V. A Hybrid Computation Model to Describe the Progression of Multiple Myeloma and Its Intra-Clonal Heterogeneity. Computation 2017, 5, 16.

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