Andersen2017 - Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development

  public model
Model Identifier
BIOMD0000000852
Short description 
This is a mathematical model investigating the role of chronic inflammation in the development and progression of myeloproliferative neoplasms (MPNs). The model describes the proliferation from stem cells to mature cells, including mutations of healthy stem cells to become malignant stem cells. The model also features a simple inflammatory coupling coping with cell death and affecting the basic model beneath.
Format
SBML (L2V4)
Related Publication
  • Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development.
  • Andersen M, Sajid Z, Pedersen RK, Gudmand-Hoeyer J, Ellervik C, Skov V, Kjær L, Pallisgaard N, Kruse TA, Thomassen M, Troelsen J, Hasselbalch HC, Ottesen JT
  • PloS one , 1/ 2017 , Volume 12 , Issue 8 , pages: e0183620 , PubMed ID: 28859112
  • Department of Science and Environment, Roskilde University, Roskilde, Denmark.
  • The chronic Philadelphia-negative myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms which ultimately may transform to acute myelogenous leukemia. Most recently, chronic inflammation has been described as an important factor for the development and progression of MPNs in the biological continuum from early cancer stage to the advanced myelofibrosis stage, the MPNs being described as "A Human Inflammation Model for Cancer Development". This novel concept has been built upon clinical, experimental, genomic, immunological and not least epidemiological studies. Only a few studies have described the development of MPNs by mathematical models, and none have addressed the role of inflammation for clonal evolution and disease progression. Herein, we aim at using mathematical modelling to substantiate the concept of chronic inflammation as an important trigger and driver of MPNs.The basics of the model describe the proliferation from stem cells to mature cells including mutations of healthy stem cells to become malignant stem cells. We include a simple inflammatory coupling coping with cell death and affecting the basic model beneath. First, we describe the system without feedbacks or regulatory interactions. Next, we introduce inflammatory feedback into the system. Finally, we include other feedbacks and regulatory interactions forming the inflammatory-MPN model. Using mathematical modeling, we add further proof to the concept that chronic inflammation may be both a trigger of clonal evolution and an important driving force for MPN disease progression. Our findings support intervention at the earliest stage of cancer development to target the malignant clone and dampen concomitant inflammation.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer

Metadata information

hasProperty (1 statement)
Mathematical Modelling Ontology Ordinary differential equation model

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

Connected external resources

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Model files
Andersen2017.xml SBML L2V4 Representation of Andersen2017 - Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development 74.35 KB Preview | Download

Additional files
Andersen2017.cps COPASI file of Andersen2017 - Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development 111.07 KB Preview | Download
Andersen2017.sedml SED-ML file of Andersen2017 - Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development 4.58 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Nov 12, 2019 2:39:26 PM
  • Last Modified: Nov 12, 2019 2:39:26 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Nov 12, 2019 2:39:26 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000852
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
s

inflammatory response 		3.61 item
y1

Neoplastic Cell ; BTO:0002312 ; C4345 		0.0 item
y0

Neoplastic Cell ; C4345 		0.0 item
a

cell ; Dead 		699.0 item
x0

hematopoietic stem cell 		10100.0 item
x1

hematopoietic stem cell ; BTO:0002312 		3.84E10 item
Reactions
Reactions Rate Parameters
=> s; a compartment*rs*a rs = 3.0E-4
y1 => a compartment*dy1*y1 dy1 = 129.0
y0 => compartment*ay*y0 ay = 1.1E-5
x1 => a compartment*dx1*x1 dx1 = 129.0
x0 => a compartment*dx0*x0 dx0 = 0.002
=> x0; s compartment*x0*rx*psi_x*s psi_x = 0.635402229467573; rx = 8.7E-4
a => ; s compartment*ea*a*s ea = 2.0E9
s => compartment*es*s es = 2.0
=> x1; x0 compartment*ax*Ax*x0 ax = 1.1E-5; Ax = 4.7E13
Curator's comment:
(added: 12 Nov 2019, 14:39:20, updated: 12 Nov 2019, 14:39:20)
Reproduced plots of Figure 2 in the original publication. Model simulated and plots produced using COPASI 4.24 (Build 197).