|
|
 Previous Article | Table of Contents | Next Article 
Blood, 1 January 2001, Vol. 97, No. 1, pp. 147-153
HEMATOPOIESIS
Impaired survival of bone marrow hematopoietic progenitor cells
in cyclic neutropenia
Andrew A. G. Aprikyan,
W.
Conrad Liles,
Elin Rodger,
Mechthild Jonas,
Emil Y. Chi, and
David C. Dale
From the Departments of Medicine and Pathology,
University of Washington School of Medicine, Seattle, WA.
Cyclic neutropenia (CN) is a congenital hematopoietic disorder
characterized by remarkably regular oscillations of blood neutrophils from near normal to extremely low levels at 21-day intervals. Recurring
episodes of severe neutropenia lead to repetitive and sometimes
life-threatening infections. To investigate the cellular mechanism of
CN, the ultrastructure and the proliferative and survival
characteristics of bone marrow-derived CD34+ early
progenitors, CD33+/CD34 myeloid progenitors,
and CD15+ neutrophil precursors from CN patients and
healthy volunteers were studied. The ultrastructural studies showed
profound apoptotic features in bone marrow progenitor cells in CN.
Colony-forming assays demonstrated a 75% decrease in the number of
early myeloid-committed colonies compared with controls. Long-term
culture-initiating cell assays demonstrated a 6-fold increase in
production of primitive progenitor cells in CN. To determine whether
accelerated apoptosis might account for the underproduction of myeloid
progenitors, the hematopoietic subpopulations were labeled with
fluorescein isothiocyanate-annexin V and analyzed by flow cytometry.
Short-term culture of CN cells resulted in apoptosis of approximately
65% of CD34+ cells, 80% of
CD33+/CD34 cells, and more than 70% of
CD15+ cells, as compared with 20%, 7%, and 15% apoptosis
in respective control subpopulations. Evidence of accelerated apoptosis
of bone marrow progenitor cells was observed in all 8 patients
participating in the study, regardless of the stage in the CN cycle in
which bone marrow aspirations were obtained. Granulocyte
colony-stimulating factor therapy of CN patients significantly improved
survival of bone marrow progenitor cells. These data indicate that
ineffective production of neutrophils is due to accelerated apoptosis
of bone marrow myeloid progenitor cells in CN.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
E. Himpe, C. Degaillier, A. Coppens, and R. Kooijman
Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway
J. Endocrinol.,
October 1, 2008;
199(1):
69 - 80.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R M James and S E Kinsey
The investigation and management of chronic neutropenia in children
Arch. Dis. Child.,
October 1, 2006;
91(10):
852 - 858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bellanne-Chantelot, S. Clauin, T. Leblanc, B. Cassinat, F. Rodrigues-Lima, S. Beaufils, C. Vaury, M. Barkaoui, O. Fenneteau, M. Maier-Redelsperger, et al.
Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register
Blood,
June 1, 2004;
103(11):
4119 - 4125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Lim and K. S.J. Elenitoba-Johnson
The Molecular Pathology of Primary Immunodeficiencies
J. Mol. Diagn.,
May 1, 2004;
6(2):
59 - 83.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Carlsson, A. A. G. Aprikyan, R. Tehranchi, D. C. Dale, A. Porwit, E. Hellstrom-Lindberg, J. Palmblad, J.-I. Henter, and B. Fadeel
Kostmann syndrome: severe congenital neutropenia associated with defective expression of Bcl-2, constitutive mitochondrial release of cytochrome c, and excessive apoptosis of myeloid progenitor cells
Blood,
May 1, 2004;
103(9):
3355 - 3361.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. A. Papadaki, A. G. Eliopoulos, T. Kosteas, C. Gemetzi, A. Damianaki, H. Koutala, J. Bux, and G. D. Eliopoulos
Impaired granulocytopoiesis in patients with chronic idiopathic neutropenia is associated with increased apoptosis of bone marrow myeloid progenitor cells
Blood,
April 1, 2003;
101(7):
2591 - 2600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Grenda, S. E. Johnson, J. R. Mayer, M. L. McLemore, K. F. Benson, M. Horwitz, and D. C. Link
Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis
Blood,
October 16, 2002;
100(9):
3221 - 3228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Ancliff, R. E. Gale, R. Liesner, I. M. Hann, and D. C. Linch
Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease
Blood,
November 1, 2001;
98(9):
2645 - 2650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
