oscillatory hematopoiesis

We study the dynamics of a model of white-blood-cell (WBC) production. The model consists of two compartmental differential equations with two discrete delays. We show that from normal to pathological parameter values, the system undergoes supercritical Hopf bifurcations and saddle-node bifurcations of limit cycles. We characterize the steady states of the system and perform a bifurcation analysis. Our results indicate that an increase in apoptosis rate of either hematopoietic stem cells or WBC precursors induces a Hopf bifurcation and an oscillatory regime takes place...

We report a case of chronic myelocytic leukemia (CML) with cyclic oscillation of platelet and leukocyte counts and attempt to elucidate the oscillatory mechanism from the standpoint of cytokine regulation of hematopoiesis. A 57-year-old woman with a diagnosis of CML exhibited platelet and white blood cell (WBC) count fluctuations of a cyclic nature. The average duration of the cycles was about 8 weeks. The patient suffered from headache, fatigue, and malaise at the peak of the cycle. The peak thrombopoietin concentration in peripheral blood coincided with a period of decrease in platelet numbers...

Cyclic oscillations in the peripheral blood platelet count were recently described in two patients with polycythemia vera (PV) receiving therapy with hydroxyurea (HU). This phenomenon can make proper HU dosing very challenging and may be especially problematic in PV patients who are at risk for thrombohemorrhagic complications. In this report, we describe four new cases of HU-associated platelet oscillations in patients with PV and extend our observations on one of the two previously reported cases. We also review cyclic thrombocytosis within the broader context of periodic hematopoiesis...

Using Lomb periodogram analysis we have quantified variations in the peripheral neutrophil and platelet counts of the cyclical neutropenia animal model-the grey collie. We found that the amplitudes of the oscillations in these two cell lineages vary concomitantly. Further, the power spectrum and the shape of the oscillations in the absolute neutrophil counts vary together with the amplitude of the oscillations. As the amplitude of the oscillations increases, the height of the second subharmonic increases, giving rise to a distorted oscillation with two peaks per cycle...

Studies have been carried out to determine the effect of bacterial infection on CSF production, CFU-C activation, and bacterial clearance by mature granulocytes in mice infected with Escherichia coli. These studies have shown that immediately after bacterial infection (5 minutes), serum colony-stimulating factor (CSF) levels and bone marrow colony-forming units in culture (CFU-C) levels are elevated. This is followed by oscillatory rises in both of these parameters and the appearance of granulocytes in the infected site...

The mechanism(s) driving cyclic hematopoiesis in human cyclic neutropenia remains unknown. Clinical trials suggest that an abnormal responsiveness of bone marrow progenitor cells to hematopoietic growth factors might cause oscillatory blood counts. Studies were performed to determine whether an abnormal responsiveness to multiple growth factors exists in this disorder and whether the defect could be shown in highly enriched populations of marrow progenitor cells. Bone marrow mononuclear cells from patients with congenital cyclic neutropenia required higher concentrations of added granulocyte-colony-stimulating factor (G-CSF) to achieve half-maximal colony growth than cells from normal subjects (478 +/- 90 pmol/L v 53 +/- 12 pmol/L, P less than ...

Hemopoiesis exhibits a variety of oscillatory phenomena. Since hemopoiesis is controlled by many feedback loops and since feedback loops are potentially oscillatory, it is possible that the observed oscillatory phenomena are the result of movement of hemopoiesis into an area of operation which favors stable oscillation. Although this hypothesis explains many of the observed phenomena and has had some predictive value, its important predictions have not yet been satisfactorily tested.