scholarly journals ASSESSMENT OF CONGENITAL NEUTROPENIA IN CHILDREN: COMMON CLINICAL SCENERIES AND CLUES FOR MANAGEMENT

2022 ◽  
Vol 14 (1) ◽  
pp. e2022008
Author(s):  
Ilaria Lazzareschi ◽  
Elena Rossi ◽  
Antonietta Curatola ◽  
Giovanna Capozio ◽  
Luca Benacquista ◽  
...  
Keyword(s):  
Hematologic Malignancy ◽  
Neutrophil Granulocytes ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Congenital Neutropenia ◽  
Cyclic Neutropenia ◽  
Hematological Diseases ◽  
Neutropenic Patients ◽  
The Many ◽  
Stimulating Factor

A disparate group of rare hematological diseases characterized by impaired maturation of neutrophil granulocytes defines congenital neutropenias. Neutropenic patients are prone to recurrent infections beginning in the first months of life. Of interest is “cyclic neutropenia”, an ultra-rare disorder revealed by sinusoidal variations of the neutrophil count and periodically-recurring infections every 21 days. Diagnosis of these disorders is frequently obscured by the multiple causes of recurrent fevers in children. Aim of this overview is to outline the physical assessment of children presenting with early-onset symptomatic neutropenia, identify the disease between the many medical conditions and even emergencies which should enter in differential diagnosis, hint at the potential management with granulocyte-colony stimulating factor, define the risk of evolution to hematologic malignancy, and summarize inter-professional team strategies for improving care coordination and outcomes of such patients.

scholarly journals Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1144-1147 ◽  
Author(s):  
U Kyas ◽  
T Pietsch ◽  
K Welte
Keyword(s):  
Binding Sites ◽  
Signal Transduction Pathway ◽  
Receptor Expression ◽  
Scatchard Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Cyclic Neutropenia ◽  
Stimulating Factor

Abstract We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G- CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.

Expression of receptors for granulocyte colony-stimulating factor on neutrophils from patients with severe congenital neutropenia and cyclic neutropenia

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1144-1147 ◽  
Author(s):  
U Kyas ◽  
T Pietsch ◽  
K Welte
Keyword(s):  
Binding Sites ◽  
Signal Transduction Pathway ◽  
Receptor Expression ◽  
Scatchard Analysis ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Severe Congenital Neutropenia ◽  
Congenital Neutropenia ◽  
Cyclic Neutropenia ◽  
Stimulating Factor

We studied granulocyte colony-stimulating factor (G-CSF) binding sites on neutrophils from patients with severe congenital neutropenia (SCN; Kostmann-syndrome) and cyclic neutropenia (CN) during treatment with recombinant human (rh) G-CSF. G-CSF receptor expression was measured by scatchard analysis. Neutrophils from six healthy controls expressed between 480 and 1,210 binding sites per cell, whereas neutrophils from five SCN patients expressed increased numbers of G-CSF binding sites ranging between 2,100 and 3,900 per cell. Neutrophils from four patients with CN expressed 350 to 1,600 binding sites per cell. The affinity of rhG-CSF to its receptor was similar in patients and controls. These data suggest that SCN patients and CN patients are not defective in G-CSF receptor expression as judged by the numbers of G- CSF binding sites and binding affinity; however, we cannot exclude defects in parts of the G-CSF receptor that may be involved in the signal transduction pathway.

Treatment of childhood-onset cyclic neutropenia with recombinant human granulocyte colony-stimulating factor

2009 ◽  
Vol 45 (2) ◽  
pp. 110-111 ◽  
Author(s):  
Koichi Sugunoto ◽  
Atsushi Togawal ◽  
Kohei Miyazono ◽  
Katsuro Itoh ◽  
Masamichi Amano ◽  
...  
Keyword(s):  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Childhood Onset ◽  
Cyclic Neutropenia ◽  
Stimulating Factor

scholarly journals Essential Role for Cyclin D3 in Granulocyte Colony-Stimulating Factor-Driven Expansion of Neutrophil Granulocytes

2006 ◽  
Vol 26 (21) ◽  
pp. 8052-8060 ◽  
Author(s):  
Ewa Sicinska ◽  
Young-Mi Lee ◽  
Judith Gits ◽  
Hirokazu Shigematsu ◽  
Qunyan Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Bone Marrow Cells ◽  
Cyclin D3 ◽  
Neutrophil Granulocytes ◽  
Neutrophil Granulocyte ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Hematopoietic Stem ◽  
Stimulating Factor

ABSTRACT The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutrophil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G1 cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation.

scholarly journals Hematopoietic progenitors in cyclic neutropenia: effect of granulocyte colony-stimulating factor in vivo

Blood ◽  
1990 ◽  
Vol 75 (10) ◽  
pp. 1951-1959 ◽  
Author(s):  
AR Migliaccio ◽  
G Migliaccio ◽  
DC Dale ◽  
WP Hammond
Keyword(s):  
Growth Factor ◽  
Progenitor Cells ◽  
Blood Cells ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Cyclic Neutropenia ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Stimulating Factor

Abstract The number and growth factor requirements of committed progenitor cells (colony-forming units-granulocyte/macrophage and burst-forming units- erythroid) in three patients with cyclic neutropenia (two congenital, one acquired) were studied before and during therapy with recombinant human granulocyte colony-stimulating factor (G-CSF; 3 to 10 micrograms/kg/d). When the patients with congenital disease were treated with G-CSF, the cycling of blood cells persisted, but the cycle length was shortened from 21 days to 14 days, and the amplitude of variations in blood counts increased. There was a parallel shortening of the cycle and increase of the amplitude of variations (from two- to three-fold to 10- to 100-fold) in the number of both types of circulating progenitor cells in these two patients. In the patient with acquired cyclic neutropenia, cycling of both blood cells and progenitors could not be seen. In cultures deprived of fetal bovine serum, erythroid and myeloid bone marrow progenitor cells from untreated patients and from normals differed in growth factor responsiveness. As examples, maximal growth of granulocyte/macrophage (GM) colonies was induced by granulocyte/macrophage (GM)-CSF plus G-CSF in the patients, whereas a combination of GM-CSF, G-CSF and interleukin- 3 (IL-3) was required in the normals, and erythropoietin alone induced fourfold more erythroid bursts from cyclic neutropenic patients than from normal donors (46% versus 11% of the maximal colony number, respectively). The growth factor responsiveness of marrow progenitor cells slightly changed during the treatment toward the values observed with normal progenitors. These results indicate that treatment with G- CSF not only ameliorated the neutropenia, but also increased the amplitude and the frequency of oscillation of circulating progenitor cell numbers. These data are consistent with the hypothesis that G-CSF therapy affects the proliferation of the hematopoietic stem cell.

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