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Blood, Vol. 92 No. 8 (October 15), 1998:
pp. 2629-2640
REVIEW ARTICLE
Cyclical Neutropenia and Other Periodic Hematological Disorders: A
Review of Mechanisms and Mathematical Models
Caroline Haurie,
David C. Dale, and
Michael C. Mackey
From the Departments of Physiology, Physics, and Mathematics, Center
for Nonlinear Dynamics in Physiology and Medicine, McGill University,
Montreal, Quebec, Canada; and the Division of Hematology, Department of
Medicine, University of Washington, Seattle, WA.
Although all blood cells are derived from hematopoietic stem cells,
the regulation of this production system is only partially understood.
Negative feedback control mediated by erythropoietin and thrombopoietin
regulates erythrocyte and platelet production, respectively, but the
regulation of leukocyte levels is less well understood. The local
regulatory mechanisms within the hematopoietic stem cells are also not
well characterized at this point. Because of their dynamic character,
cyclical neutropenia and other periodic hematological disorders offer a
rare opportunity to more fully understand the nature of these
regulatory processes. We review the salient clinical and laboratory
features of cyclical neutropenia (and the less common disorders
periodic chronic myelogenous leukemia, periodic auto-immune hemolytic
anemia, polycythemia vera, aplastic anemia, and cyclical
thrombocytopenia) and the insight into these diseases afforded by
mathematical modeling. We argue that the available evidence indicates
that the locus of the defect in most of these dynamic diseases is at
the stem cell level (auto-immune hemolytic anemia and cyclical
thrombocytopenia seem to be the exceptions). Abnormal responses to
growth factors or accelerated cell loss through apoptosis may play an
important role in the genesis of these disorders.
© 1998 by The American Society of Hematology.
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