scholarly journals Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1919-1922 ◽  
Author(s):  
K Mempel ◽  
T Pietsch ◽  
T Menzel ◽  
C Zeidler ◽  
K Welte
Keyword(s):  
Serum Levels ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Maturation Arrest ◽  
Kostmann Syndrome ◽  
Stimulating Factor ◽  
Normal Controls ◽  
Csf Production

Severe congenital neutropenia (SCN), also known as Kostmann Syndrome, is characterized by a maturation arrest of myelopoiesis at the level of promyelocytes with absence of neutrophils in bone marrow (BM) and blood. Hypotheses of the pathophysiology of SCN include (1) defective production of granulocyte colony-stimulating factor (G-CSF), and/or (2) defective response to G-CSF. To exclude defective G-CSF production we tested sera from patients with SCN for the presence of G-CSF using Western blot analysis and NFS-60 proliferation assay. Using these assays we were able to detect increased G-CSF serum levels in SCN patients (150 to 910 pg/mL) as compared with normal controls (between undetectable and 100 pg/mL). These results suggest that patients with SCN have no defect in G-CSF production but a defective response of neutrophil precursors to endogenous G-CSF.

scholarly journals Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia

Blood ◽  
1991 ◽  
Vol 77 (9) ◽  
pp. 1919-1922 ◽  
Author(s):  
K Mempel ◽  
T Pietsch ◽  
T Menzel ◽  
C Zeidler ◽  
K Welte
Keyword(s):  
Serum Levels ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Maturation Arrest ◽  
Kostmann Syndrome ◽  
Stimulating Factor ◽  
Normal Controls ◽  
Csf Production

Abstract Severe congenital neutropenia (SCN), also known as Kostmann Syndrome, is characterized by a maturation arrest of myelopoiesis at the level of promyelocytes with absence of neutrophils in bone marrow (BM) and blood. Hypotheses of the pathophysiology of SCN include (1) defective production of granulocyte colony-stimulating factor (G-CSF), and/or (2) defective response to G-CSF. To exclude defective G-CSF production we tested sera from patients with SCN for the presence of G-CSF using Western blot analysis and NFS-60 proliferation assay. Using these assays we were able to detect increased G-CSF serum levels in SCN patients (150 to 910 pg/mL) as compared with normal controls (between undetectable and 100 pg/mL). These results suggest that patients with SCN have no defect in G-CSF production but a defective response of neutrophil precursors to endogenous G-CSF.

Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2947-2953 ◽  
Author(s):  
Brigitte Kasper ◽  
Nicola Tidow ◽  
Dirk Grothues ◽  
Karl Welte
Keyword(s):  
Superoxide Anion ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Maturation Arrest ◽  
Guanosine Diphosphate ◽  
Kostmann Syndrome ◽  
Gdp Dissociation Inhibitor ◽  
Stimulating Factor

Severe congenital neutropenia (SCN) or Kostmann syndrome is a disorder of myelopoiesis characterized by a maturation arrest at the stage of promyelocytes or myelocytes in bone marrow and absolute neutrophil counts less than 200/μL in peripheral blood. Treatment of these patients with granulocyte colony-stimulating factor (G-CSF) leads to a significant increase in circulating neutrophils and a reduction in infection-related events in more than 95% of the patients. To date, little is known regarding the underlying pathomechanism of SCN. G-CSF-induced neutrophils of patients with SCN are functionally defective (eg, chemotaxis, superoxide anion generation, Ca++mobilization). Two guanosine triphosphatases (GTPases), Rac2 and RhoA, were described to be involved in many neutrophil functions. The expression of these GTPases and their regulation in patients' neutrophils were of interest. This study determined that the guanosine diphosphate (GDP)-dissociation inhibitor RhoGDI is overexpressed at the protein level in patients' neutrophils and that overexpression is a result of G-CSF treatment. RhoA and LyGDI are expressed at similar levels, whereas Rac2 shows a decreased expression. In addition, association of Rac2 and RhoGDI or LyGDI is abrogated or not detectable based on the low Rac2 expression in patients' neutrophils.

scholarly journals Blood mononuclear cells from patients with severe congenital neutropenia are capable of producing granulocyte colony-stimulating factor

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1234-1237 ◽  
Author(s):  
T Pietsch ◽  
C Buhrer ◽  
K Mempel ◽  
T Menzel ◽  
U Steffens ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Leukemia Cell Line ◽  
Severe Neutropenia ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Blood Mononuclear Cells ◽  
Stimulating Factor

Abstract Severe congenital neutropenia (SCN) is a disorder of myelopoiesis characterized by severe neutropenia or absence of blood neutrophils secondary to a maturational arrest at the level of promyelocytes. We examined peripheral blood mononuclear cells (PBMC) of SCN patients who demonstrated normalization of their blood neutrophil counts in a phase II clinical study with recombinant human granulocyte colony-stimulating factor (rhG-CSF). When stimulated in vitro with bacterial lipopolysaccharides (LPS), PBMC of those SCN patients produced G-CSF activity, as judged by proliferation induction of the murine leukemia cell line, NFS-60. Western and Northern blot analysis showed G-CSF protein and G-CSF-mRNA indistinguishable in size from those of normal controls. We conclude that PBMC of the SCN patients tested are capable of synthesizing and secreting biologically active G-CSF in vitro.

Spontaneous remission of granulocyte colony-stimulating factor–associated leukemia in a child with severe congenital neutropenia

Blood ◽  
2000 ◽  
Vol 96 (10) ◽  
pp. 3647-3649 ◽  
Author(s):  
Sima Jeha ◽  
Ka Wah Chan ◽  
Andrew G. Aprikyan ◽  
W. Keith Hoots ◽  
Steven Culbert ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Allogeneic Bone Marrow Transplantation ◽  
Spontaneous Remission ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Stimulating Factor

Leukemia is observed with increased frequency in patients with severe congenital neutropenia (SCN). In the past decade, recombinant human granulocyte colony-stimulating factor (rh G-CSF) has prolonged the survival of patients with SCN increasingly reported to have leukemias. In this communication acute myelogenous leukemia (AML) associated with a mutation of the G-CSF receptor (G-CSF-R) developed in a patient with SCN maintained on long-term G-CSF therapy. The blast count in the blood and bone marrow fell to undetectable levels twice on withholding G-CSF and without chemotherapy administration, but the mutant G-CSF-R was detectable during this period. The patient subsequently underwent successful allogeneic bone marrow transplantation. After transplantation, the patient's neutrophil elastase (ELA-2) mutation and G-CSF-R mutation became undetectable by polymerase chain reaction. This report provides novel insights on leukemia developing in congenital neutropenia.

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