Observations on the Pathophysiology and Mechanisms for Cyclic Neutropenia

Colijn, Caroline; Dale, David C.; Foley, Catherine; Mackey, Michael C.

doi:10.1051/mmnp:2008004

Cited by 9 publications

(8 citation statements)

References 60 publications

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“…Our model suggests that both scenarios can exist. In some cases stem cell properties (a 1 , p 1 , d 1 ) differ from their physiologic reference values (Constellations 1-5 and 8,9), whereas in other cases they do not (Constellations 6 and 7).…”

Section: Formentioning

confidence: 96%

Oscillations in a white blood cell production model with multiple differentiation stages

2019

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In this work we prove occurrence of a super-critical Hopf bifurcation in a model of white blood cell formation structured by three maturation stages. We provide an explicit analytical expression for the bifurcation point depending on model parameters. The Hopf bifurcation is a unique feature of the multi-compartment structure as it does not exist in the corresponding two-compartment model. It appears for a parameter set different from the parameters identified for healthy hematopoiesis and requires changes in at least two cell properties. Model analysis allows identifying a range of biologically plausible parameter sets that can explain persistent oscillations of white blood cell counts observed in some hematopoietic diseases. Relating the identified parameter sets to recent experimental and clinical findings provides insights into the pathological mechanisms leading to oscillating blood cell counts.

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Section: Formentioning

confidence: 96%

Oscillations in a white blood cell production model with multiple differentiation stages

2019

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“…We digitized data from Wang et al [72] for the circulating platelet and TPO levels in healthy patients following a 1 µg/kg of bodyweight intravenous infusion of Romiplostim, a TPO mimetic with similar physiological activity to TPO. We then fitted the parameters by simulating the response of our model (11)- (14) to an infusion of 1 µg/kg of TPO and minimizing the squared error between data and simulation.…”

Section: A42 Thrombopoietin Compartmentmentioning

confidence: 99%

Normal and pathological dynamics of platelets in humans

et al. 2017

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We develop a mathematical model of platelet, megakaryocyte, and thrombopoietin dynamics in humans. We show that there is a single stationary solution that can undergo a Hopf bifurcation, and use this information to investigate both normal and pathological platelet production, specifically cyclic thrombocytopenia. Carefully estimating model parameters from laboratory and clinical data, we then argue that a subset of parameters are involved in the genesis of cyclic thrombocytopenia based on clinical information. We provide model fits to the existing data for both platelet counts and thrombopoietin levels by changing four parameters that have physiological correlates. Our results indicate that the primary change in cyclic thrombocytopenia is an interference with, or destruction of, the thrombopoietin receptor with secondary changes in other processes, including immune-mediated destruction of platelets and megakaryocyte deficiency and failure in platelet production. This study contributes to the understanding of the origin of cyclic thrombocytopenia as well as extending the modeling of thrombopoiesis.

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“…The importance of delayed negative feedback in granulopoiesis has been highlighted in seminal works on CN [10,25,36]. Mathematical models have been used to represent cyclic oscillations in absolute neutrophil counts (see comprehensive reviews for mathematical modeling and analysis, [10,25,36]). Although mutation in ELANE gene is predominant in human severe congenital neutropenia (SCN), mice expressing a neutrophil elastase mutation have normal granulopoiesis [30].…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant human G-CSF (rhG-CSF) can be used as a therapeutic drug for patients with SCN and CN. Although it is not possible to completely cure congenital neutropenia, the use of G-CSF temporally recovers the number of neutrophils [10].…”

Section: Introductionmentioning

confidence: 99%

Mathematical study on kinetics of hematopoietic stem cells – theoretical conditions for successful transplantation

Nakaoka

Aihara

2012

Journal of Biological Dynamics

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Numerous haematological diseases occur due to dysfunctions during homeostasis processes of blood cell production. Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for the treatment of haematological malignancy and congenital immunodeficiency. Today, HSCT is widely applied as an alternative method to bone marrow transplantation; however, HSCT can be a risky procedure because of potential side effects and complications after transplantations. Although an optimal regimen to achieve successful HSCT while maintaining quality of life is to be developed, even theoretical considerations such as the evaluations of successful engraftments and proposals of clinical management strategies have not been fully discussed yet.In this paper, we construct and investigate mathematical models that describe the kinetics of hematopoietic stem cell self-renewal and granulopoiesis under the influence of growth factors. Moreover, we derive theoretical conditions for successful HSCT, primarily on the basis of the idea that the basic reproduction number R 0 represents a threshold condition for a population to successfully grow in a given steady-state environment. Successful engraftment of transplanted haematopoietic stem cells (HSCs) is subsequently ensured by employing a concept of dynamical systems theory known as 'persistence'. On the basis of the implications from the modelling study, we discuss how the conditions derived for a successful HSCT are used to link to experimental studies.

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Observations on the Pathophysiology and Mechanisms for Cyclic Neutropenia

Abstract: Abstract. We review the basic pathology of cyclical neutropenia in both humans and the grey collie, and examine the role that mathematical modeling of hematopoietic cell production has played in our understanding of the origins of this fascinating dynamical disease.

Cited by 9 publications

References 60 publications

Oscillations in a white blood cell production model with multiple differentiation stages

Oscillations in a white blood cell production model with multiple differentiation stages

Normal and pathological dynamics of platelets in humans

Mathematical study on kinetics of hematopoietic stem cells – theoretical conditions for successful transplantation

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