These results explain the molecular basis for G-CSFR mutations in the pathogenesis of the dominant-negative phenotype and hypersensitivity to G-CSF in SCN/AML.
Defective internalization and sustained activation of truncated granulocyte colony-stimulating factor receptor found in severe congenital neutropenia/acute myeloid leukemia.
These results suggest that primitive myeloid progenitor cells of patients with SCN have defective responsiveness to not only G-CSF, but also the early- or intermediate-acting hematopoietic factors, SF, FL, and IL-3.
Novel point mutation in the extracellular domain of the granulocyte colony-stimulating factor (G-CSF) receptor in a case of severe congenital neutropenia hyporesponsive to G-CSF treatment.
Recently, studies of patients with SCN who subsequently developed acute myeloid leukemia (AML) revealed nonsense mutations in the cytoplasmic domain of the granulocyte colony-stimulating factor (G-CSF) receptor messenger RNA.
These results explain the molecular basis for G-CSFR mutations in the pathogenesis of the dominant-negative phenotype and hypersensitivity to G-CSF in SCN/AML.
Sustained receptor activation and hyperproliferation in response to granulocyte colony-stimulating factor (G-CSF) in mice with a severe congenital neutropenia/acute myeloid leukemia-derived mutation in the G-CSF receptor gene.
Expression of the SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2 was analyzed in myeloid cells from patients with SCN in comparison to healthy donors.
Whereas SHP-1 and SHP-2 were hardly detectable in neutrophils from healthy donors, neutrophils from patients with SCN revealed high amounts of these two proteins in Western blot analyses.
Expression of the SH2 domain-containing tyrosine phosphatases SHP-1 and SHP-2 was analyzed in myeloid cells from patients with SCN in comparison to healthy donors.
These results demonstrate that the presence of qualitative and quantitative abnormalities of primitive myeloid progenitor cells expressing G-CSFR may play an important role in the impairment of granulopoiesis in patients with SCN.(Blood.2000;96:4366-4369)
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.
To address this issue, we studied a child with SCN who was totally unresponsive to G-CSF and had a novel point mutation in the extracellular domain of the G-CSF receptor (GCSF-R).
Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis.
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.
These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5.
These data provide insight into SCN unresponsive to standard G-CSF treatment and to the potential corrective action of combined treatment with G-CSF and corticosteroids through synergistic activation of STAT5.
Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia.
Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia.