Research article Special Issues

Mathematical analysis of the Cancitis model and the role of inflammation in blood cancer progression

  • Received: 30 May 2019 Accepted: 04 September 2019 Published: 16 September 2019
  • Recently, a tight coupling has been observed between inflammation and blood cancer such as the Myeloproliferative Neoplasms (MPNs). A mechanism based six-dimensional model-the Cancitis model-describing the progression of blood cancer coupled to the inflammatory system is analyzed. An analytical investigation provides criteria for the existence of physiological steady states, trivial, hematopoietic, malignant and co-existing steady states. The classification of steady states is explicitly done in terms of the inflammatory stimuli. Several parameters are crucial in determining the attracting steady state(s). In particular, increasing inflammatory stimuli may transform a healthy state into a malignant state under certain circumstances. In contrast for the co-existing steady state, increasing inflammatory stimuli may reduce the malignant cell burden. The model provides an overview of the possible dynamics which may inform clinical practice such as whether to use inflammatory inhibitors during treatment.

    Citation: Zamra Sajid, Morten Andersen, Johnny T. Ottesen. Mathematical analysis of the Cancitis model and the role of inflammation in blood cancer progression[J]. Mathematical Biosciences and Engineering, 2019, 16(6): 8268-8289. doi: 10.3934/mbe.2019418

    Related Papers:

  • Recently, a tight coupling has been observed between inflammation and blood cancer such as the Myeloproliferative Neoplasms (MPNs). A mechanism based six-dimensional model-the Cancitis model-describing the progression of blood cancer coupled to the inflammatory system is analyzed. An analytical investigation provides criteria for the existence of physiological steady states, trivial, hematopoietic, malignant and co-existing steady states. The classification of steady states is explicitly done in terms of the inflammatory stimuli. Several parameters are crucial in determining the attracting steady state(s). In particular, increasing inflammatory stimuli may transform a healthy state into a malignant state under certain circumstances. In contrast for the co-existing steady state, increasing inflammatory stimuli may reduce the malignant cell burden. The model provides an overview of the possible dynamics which may inform clinical practice such as whether to use inflammatory inhibitors during treatment.


    加载中


    [1] P. J. Campbell and A. R. Green, The myeloproliferative disorders, N. Engl. J. Med., 355 (2006), 2452-2466.
    [2] H. C. Hasselbalch, Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?, Leukemia Res., 37 (2013), 214-220.
    [3] H. C. Hasselbalch, Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis: is chronic inflammation a trigger and driver of clonal evolution and development of accelerated atherosclerosis and second cancer?, Blood, 119 (2012), 3219- 3226.
    [4] S. Y. Kristinsson, O. Landgren, J. Samuelsson, et al., Autoimmunity and the risk of myeloproliferative neoplasms, Haematologica, 95 (2010), 1216-1220.
    [5] M. Andersen, Z. Sajid, R. K. Pedersen, et al., Mathematical modelling as a proof of concept for MPNs as a human inflammation model for cancer development, Plos One, 12 (2017), 1-18.
    [6] T. Barbui, A. Carobbio, G. Finazzi, et al., Inflammation and thrombosis in essential thrombocythemia and polycythemia vera: different role of C-reactive protein and pentraxin 3, Haematologica, 96 (2011), 315-318.
    [7] N. L. Komarova, Principles of regulation of self-renewing cell lineages, Plos One, 8 (2013).
    [8] N. L. Komarova and P. van den Driessche, Stability of control networks in autonomous homeostatic regulation of stem cell lineages, B. Math. Biol., 80 (2015), 1345-1365.
    [9] J. Yang, D. E. Axelrod and N. L. Komarova, Determining the control networks regulating stem cell lineages in colonic crypts, J. Theor. Biol., 429 (2017), 190-203.
    [10] F. Michor, Y. Iwasa and M. A. Nowak, Dynamics of cancer progression, Nature Rev. Cancer, 4 (2004), 197-205.
    [11] F. Michor, T. P. Hughes, Y. Iwasa, et al., Dynamics of chronic myeloid leukaemia, Nature, 435 (2005), 1267-1270.
    [12] D. Dingli and F. Michor, Successful Therapy Must Eradicate Cancer Stem Cells, Stem Cells, 24 (2006), 2603-2610.
    [13] G. Clapp, T. Lepoutre, R. El Cheikh, et al., Implication of autologousimmune system in bcr-abl transcript variations in chronic myelogenous leukemia patients treated with imatinib, Cancer Res., 75 (2015), 4053-4062.
    [14] T. Stiehl and A. Marciniak-Czochra, Mathematical modelling of leukemogenesis and cancer stem cell dynamics, Math. Model. Nat. Phenom., 7 (2012), 166-202.
    [15] T. Stiehl, A. D. Ho and A. Marciniak-Czochra, Mathematical modelling of the impact of cytokine response of acute myeloid leukemia cells on patient prognosis, Sci. Rep., 2809 (2018).
    [16] H. Haeno, R. L. Levine, D. G. Gilliland, et al., A progenitor cell origin of myeloid malignancies, Proc. Natl. Acad. Sci. USA, 106 (2009), 16616-16621.
    [17] J. Zhang, A. G. Fleischman, D. Wodarz, et al., Determining the role of infammation in the selection of JAK2 mutant cells in myeloproliferative neoplasms, J. Theor. Biol., 425 (2017), 43-52.
    [18] J. T. Ottesen, Z. Sajid, R. K. Pedersen, et al., Bridging blood cancers and inflammation: The reduced Cancitis model, J. Theor. Biol., 465 (2019), 90-108.
    [19] C. Walkley, J. Shea, N. Sims, et al., Rb regulates interactions between hematopoietic stem cells and their bone marrow microenvironment, Cell, 129 (2007), 1081-1095.
    [20] T. Stiehl, N. Baran, A. D. Ho, et al., Cell division patterns in acute myeloid leukemia stem-like cells determine clinical course: A model to predict patient survival, Cancer Res., 75 (2015), 940-949.
    [21] T. Walenda, T. Stiehl, H. Braun, et al., Feedback Signals in Myelodysplastic Syndromes: Increased Self-Renewal of the Malignant Clone Suppresses Normal Hematopoiesis, PLoS Comput. Biol., 10 (2014), e1003599.
    [22] Y. W. Kim, B. K. Koo, H. W. Jeong, et al., Defective Notch activation in microenvironment leads to myeloproliferative disease, Blood, 112 (2008), 4628-4638. doi: 10.1182/blood-2008-03-148999
    [23] K. Y. King and M. A. Goodell, Inflammatory modulation of hematopoietic stem cells: viewing the hematopoietc stem cell as a foundation for the immune response, Nat. Rev. Immmunol., 11 (2014), 685-692.
    [24] E. Rovida, I. Marzi, M. G. Cipolleschi, et al., One more stem cell niche: how the sensitivity of chronic myeloid leukemia cells to imatinib mesylate is modulated within a "hypoxic" environment, Hypoxia, (2014), 1-10.
    [25] A. Marciniak-Czochra, T. Stiehl, A. D. Ho, et al., Modeling of asymmetric cell division in hematopoietic stem cells-regulation of self-renewal is essential for efficient repopulation, Stem Cells Dev., 18 (2009), 377-385.
    [26] A. L. Jackson and L. A. Loeb, The mutation rate and cancer, Eur. J. Haematol., 97 (2016), 63-69.
    [27] A. Knutson, Mutation and Cancer: Statistical study of retinoblastoma, Proc. Natl. Acad. Sci. USA, 68 (1971), 820-823.
    [28] F. Michor, Y. Iwasa and N. MA, The age incidence of chronic myeloid leukemia can be explained by a one-mutation model, Proc. Natl. Acad. Sci. USA, 103 (2006), 14931-14934.
    [29] F. Michor, Mathematical models of cancer stem cells, J. Clin. Oncol., 26 (2008), 2854-2861.
    [30] E. Voit, A first course in system biology, Garland Science, Taylor & Francis Group, New York and London, 68 (2013).
    [31] A. L. Sørensen and H. C. Hasselbalch, Smoking and Philadelphia-negative chronic myeloproliferative neoplasms, Genetics, 148 (1998), 1483-1490.
    [32] H. C. Hasselbalch, Smoking as a contributing factor for development of polycythemia vera and related neoplasms, Leukemia Res., 015 (2015).
    [33] V. A. Kuznetsov and G. D. Knott, Modeling tumor regrowth and immunotherapy, Math. Comput. Model., 33 (2001), 1275-1287.
    [34] C. Robinson, Dynamical Systems, Stability, Symbolic Dynamics, and Chaos, in Second CRC Press, Boca Raton, Fla., 1999.
  • Reader Comments
  • © 2019 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(3996) PDF downloads(595) Cited by(4)

Article outline

Figures and Tables

Figures(4)  /  Tables(3)

Other Articles By Authors

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog