Periodic Hematopoiesis in Human Cyclic Neutropenia

Guerry, DuPont; Dale, David C.; Omine, Mitsuhiro; Perry, Seymour; Wolff, Sheldon M.

doi:10.1172/jci107522

Cited by 138 publications

(67 citation statements)

References 35 publications

(33 reference statements)

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“…In most patients, neutrophil levels oscillate, with a typical period of 19 to 21 days, between 2.0 × 10 9 cells/L at the peaks to lows of almost zero. The count nadir usually lasts for 2 to 4 days and more severe symptoms are associated with extremely low blood neutrophil levels for longer periods, up to 40 days [37,48,51]. Cycling of blood monocytes from normal levels to about two or three times normal also occurs regularly with the peaks of monocytes corresponding closely to the nadir of blood neutrophils.…”

Section: Cyclical Neutropeniamentioning

confidence: 99%

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Delay Differential Equations and Autonomous Oscillations in Hematopoietic Stem Cell Dynamics Modeling

Adimy

Crauste

2012

Math. Model. Nat. Phenom.

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Abstract. We illustrate the appearance of oscillating solutions in delay differential equations modeling hematopoietic stem cell dynamics. We focus on autonomous oscillations, arising as consequences of a destabilization of the system, for instance through a Hopf bifurcation. Models of hematopoietic stem cell dynamics are considered for their abilities to describe periodic hematological diseases, such as chronic myelogenous leukemia and cyclical neutropenia. After a review of delay models exhibiting oscillations, we focus on three examples, describing different delays: a discrete delay, a continuous distributed delay, and a state-dependent delay. In each case, we show how the system can have oscillating solutions, and we characterize these solutions in terms of periods and amplitudes.

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Section: Cyclical Neutropeniamentioning

confidence: 99%

“…The oscillations in other cell types such as platelets, lymphocytes and reticulocytes, are usually marked by irregularity and high frequency noise (Guerry et al [48]). The origins of oscillations in CN are unclear.…”

Section: Cyclical Neutropeniamentioning

confidence: 99%

Delay Differential Equations and Autonomous Oscillations in Hematopoietic Stem Cell Dynamics Modeling

Adimy

Crauste

2012

Math. Model. Nat. Phenom.

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“…Cyclic neutropenia is attributable to oscillatory production of neutrophils and other blood cells by the bone marrow, manifested in the cycling of circulating blood cells [2,17]. This marrow abnormality is due to defective neutrophil formation with interruption of cell production at the promyelocyte-myelocyte stage, the stage in neutrophil development when the enzyme neutrophil elastase is normally synthesized and packaged in the neutrophil granules [18].…”

Section: Pathophysiologymentioning

confidence: 99%

“…In patients with cyclic neutropenia, bone marrow aspiration or biopsy at the onset of severe neutropenia characteristically shows a deficiency of cells in the late stage of neutrophil development [17]. There are fewer than normal myelocytes, metamylocytes, bands and mature neutrophils, a condition often referred to as "maturation arrest."…”

Section: Pathophysiologymentioning

confidence: 99%

“…Severe congenital neutropenia is also treatable with G-CSF, but it is less responsive, requiring high doses of G-CSF. In addition, SCN may evolve to acute myeloid leukemia [16,17]. Some patients with severe congenital neutropenia have oscillations in their blood neutrophils and these oscillations are more easily detected when they receive G-CSF therapy [24].…”

Section: Comparisons Of Cyclic Neutropenia and Severe Congenital Neutmentioning

confidence: 99%

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Observations on the Pathophysiology and Mechanisms for Cyclic Neutropenia

Colijn

Dale

Foley

et al. 2006

Math. Model. Nat. Phenom.

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Chronobiology in hematology and immunology

et al. 1983

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The hematopoietic and the immune systems in all their components are characterized by a multifrequency time structure with prominent rhythms in cell proliferation and cell function in the circadian, infradian, and rhythms in cell proliferation and cell function in the circadian, infradian, and circannual frequency ranges. The circulating formed elements in the peripheral blood show highly reproducible circadian rhythms. The timing and the extent of these rhythms were established in a clinically healthy human population and are shown as chronograms, cosinor summaries and, for some high-amplitude rhythms, as time-qualified reference ranges (chronodesms). Not only the number but also the reactivity of circulating blood cells varies predictably as a function of time as shown for the circadian rhythm in responsiveness of human and murine lymphocytes in vitro to lectin mitogens (phytohemagglutinin and pokeweed mitogen). Some circadian rhythms of hematologic functions appear to be innate and are presumably genetically determined but are modulated and adjusted in their timing by environmental factors, so-called synchronizers. Phase alterations in the circadian rhythms of hematologic parameters of human subjects and of mice by manipulation of the activity-rest or light-dark schedule and/or of the time of food uptake are presented. Characteristically these functions do not change their timing immediately after a shift in synchronizer phase but adapt over several and in some instances over many transient cycles. The circadian rhythm of cell proliferation in the mammalian bone marrow and lymphoid system as shown in mice in vivo and in vitro may lend itself to timed treatment with cell-cycle-specific and nonspecific agents in an attempt to maximize the desired and to minimize the undesired treatment effects upon the marrow. Differences in response, and susceptibility of cells and tissues at different stages of their circadian and circaseptan (about 7-day) rhythms and presumably of cyclic variations in other frequencies are expected to lead to the development of a chronopharmacology of the hematopoietic and immune system. Infradian rhythms of several frequencies have been described for numerous hematologic and immune functions. Some of these, i.e., in the circaseptan frequency range, seem to be of importance for humoral and for cell mediated immune functions including allograft rejection. Infradian rhythms with periods of 19 to 22 days seem to occur in some hematologic functions and are very prominent in cyclic neutropenia and (with shorter periods) in its animal model, the grey collie syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

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Periodic Hematopoiesis in Human Cyclic Neutropenia

Cited by 138 publications

References 35 publications

Delay Differential Equations and Autonomous Oscillations in Hematopoietic Stem Cell Dynamics Modeling

Delay Differential Equations and Autonomous Oscillations in Hematopoietic Stem Cell Dynamics Modeling

Observations on the Pathophysiology and Mechanisms for Cyclic Neutropenia

Chronobiology in hematology and immunology

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