Neutropenia dynamics in a case of T‐LGL lymphoproliferation illustrate rapid turnover of granulocyte progenitors

Wolfrom, C.; Lévy, Vincent; Deschatrette, Jean

doi:10.1111/j.1365-2184.2010.00678.x

Cited by 3 publications

(5 citation statements)

References 23 publications

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“…A critical issue is to be able to affirm that the observed convergence of bisecting lines in various proliferation series is a consequence solely of chaotic dynamics; this is particularly important because there always are some stochastic components in experimental data. In our previous experimental observations, we checked the dispersion (means and sd) of the intersections, and used the Monte-Carlo technique of surrogate data to help distinguish between random and deterministic fluctuations [14] – [16, and Appendix S1 ]. Mathematicians in the field exploit various techniques of analysis involving either surrogate data [22] , [23] , or the forecasting error technique [24] , or the confinement technique [25] , with extended series of data to affirm the chaotic or stochastic nature of fluctuations.…”

Section: Discussionmentioning

confidence: 99%

“…Using this method, we detected a deterministic structure, an attracting fixed-point, in various time-series, both in vitro and in vivo . We detected such focal points in: i) the cultured rat liver cancer cell line Fao, which is clonal in origin [14] ; ii) various series of primary cultures of mouse bone marrow cells, and in their derived blood progenitors [15] ; and iii) circulating human neutrophils in vivo , in a patient presenting with a T-cell lymphoma [16] . In cultured cells, experimental culture conditions were kept as constant as possible.…”

Section: Introductionmentioning

confidence: 99%

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Unmasking Chaotic Attributes in Time Series of Living Cell Populations

2010

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BackgroundLong-range oscillations of the mammalian cell proliferation rate are commonly observed both in vivo and in vitro. Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.Methodology/Principal FindingsUsing a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.Conclusion/SignificanceTheoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

2010

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“…The extent of leukemic LGL infiltration in the bone marrow does not correlate with degree of cytopenia. Analysis of the neutrophil population in a T-LGL leukemia patient with neutropenia showed that a decrease of neutrophil count caused by TLGLs is balanced by pulses of compensatory neutrophils production [58].…”

Section: Potential Mechanisms Of Cytopenias In T/natural Killer-largementioning

confidence: 99%

Advances in diagnosis and treatment of large granular lymphocyte syndrome

Prochorec‐Sobieszek

2011

Current Opinion in Hematology

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“…LGLL patients are characterized by a heterogenous clinical course. They may remain asymptomatic for a long time, but roughly 2/3 of them develop symptoms during the natural history of the disease, with 30-70% of cases requiring therapy [50,74,75]. According to current concepts, treatment of LGLL patients is required in the presence of symptomatic or severe (ANC < 0.5 × 10 9 /L) neutropenia, symptomatic or transfusion-dependent anemia and associated autoimmune conditions [76].…”

Section: Treatment Indications For Neutropenic Lgll Patientsmentioning

confidence: 99%

“…Both MTX and CyA can be maintained indefinitely, according to their tolerance. In contrast, CTX should not be used for periods longer than 6-12 months because of its mutagenic potential [75]. Regardless of the treatment status, patients should be routinely monitored for symptoms and disease progression.…”

Section: Immunosuppressive Therapymentioning

confidence: 99%

Neutropenia and Large Granular Lymphocyte Leukemia: From Pathogenesis to Therapeutic Options

Calabretto

Teramo

Barilà

et al. 2021

Cells

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Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder characterized by the clonal expansion of cytotoxic T-LGL or NK cells. Chronic isolated neutropenia represents the clinical hallmark of the disease, being present in up to 80% of cases. New advances were made in the biological characterization of neutropenia in these patients, in particular STAT3 mutations and a discrete immunophenotype are now recognized as relevant features. Nevertheless, the etiology of LGLL-related neutropenia is not completely elucidated and several mechanisms, including humoral abnormalities, bone marrow infiltration/substitution and cell-mediated cytotoxicity might cooperate to its pathogenesis. As a consequence of the multifactorial nature of LGLL-related neutropenia, a targeted therapeutic approach for neutropenic patients has not been developed yet; moreover, specific guidelines based on prospective trials are still lacking, thus making the treatment of this disorder a complex and challenging task. Immunosuppressive therapy represents the current, although poorly effective, therapeutic strategy. The recent identification of a STAT3-mediated miR-146b down-regulation in neutropenic T-LGLL patients emphasized the pathogenetic role of STAT3 activation in neutropenia development. Accordingly, JAK/STAT3 axis inhibition and miR-146b restoration might represent tempting strategies and should be prospectively evaluated for the treatment of neutropenic LGLL patients.

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Neutropenia dynamics in a case of T‐LGL lymphoproliferation illustrate rapid turnover of granulocyte progenitors

Abstract: These findings illustrate how the deleterious effect of T-LGL on neutrophils is balanced, over periods of years, by pulses of compensatory neutrophil production, potentially accounting for the commonly observed prolonged indolent course of the disease.

Cited by 3 publications

References 23 publications

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

Unmasking Chaotic Attributes in Time Series of Living Cell Populations

Advances in diagnosis and treatment of large granular lymphocyte syndrome

Neutropenia and Large Granular Lymphocyte Leukemia: From Pathogenesis to Therapeutic Options

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