CYCLICAL NEUTROPENIA AND OTHER PERIODIC HEMATOLOGICAL DISORDERS - A REVIEW OF MECHANISMS AND MATHEMATICAL-MODELS

Although all blood cells are derived from hematopoietic stem cells, th e regulation of this production system is only partially understood. N egative 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 regu latory mechanisms within the hematopoietic stem cells are also not wel l characterized at this point. Because of their dynamic character, cyc lical neutropenia and other periodic hematological disorders offer a r are opportunity to more fully understand the nature of these regulator y 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, polycythe mia vera, aplastic anemia, and cyclical thrombocytopenia) and the insi ght into these diseases afforded by mathematical modeling. We argue th at the available evidence indicates that the locus of the defect in mo st of these dynamic diseases is at the stem cell level (autoimmune hem olytic anemia and cyclical thrombocytopenia seem to be the exceptions) . Abnormal responses to growth factors or accelerated cell loss throug h apoptosis may play an important role in the genesis of these disorde rs. (C) 1998 by The American Society of Hematology.