Abnormal responsiveness of granulocyte-committed progenitor cells in cyclic
neutropenia
WP Hammond, GS Chatta, RG Andrews and DC Dale
Department of Medicine, University of Washington, School of Medicine,
Seattle.
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 .01). Patients also differed in requirement for
granulocyte-macrophage- CSF (P less than .05), but not for interleukin-3 (P
greater than .30). CD34+ bone marrow cells from three patients also showed
this difference in G-CSF responsiveness (P less than .05). These data
suggest that the defect in congenital cyclic hematopoiesis lies in growth
factor receptor binding or the postreceptor signal transduction system that
drives granulocytopoiesis.
Volume 79,
Issue 10,
pp. 2536-2539,
05/15/1992
Copyright © 1992 by The American Society of Hematology
