Here we report the identification of a somatic point mutation in one allele of the G-CSF receptor gene in a patient with severe congenital neutropenia.
Mutations in the gene for the G-CSF receptor that interrupt signals required for the maturation of myeloid cells are involved in the pathogenesis of severe congenital neutropenia and associated with the progression to acute myeloid leukemia.
In this review we summarize the current knowledge of the function of the G-CSF receptor in normal granulopoiesis, as well as in some patients with severe congenital neutropenia and acute myeloblastic leukemia, diseases characterized by disturbed myeloid maturation.
Severe congenital neutropenia terminating in acute myeloid leukemia: disease progression associated with mutations in the granulocyte-colony stimulating factor receptor gene.
We investigated the frequency of these specific G-CSF receptor mutations in patients with congenital neutropenia undergoing treatment with r-metHuG-CSF (Filgrastim) and the clinical relevance of these mutations.
We present the results of a search among 20 additional cases of congenital neutropenia (CN) and SCN for the presence of mutations in the cytoplasmic domain of G-CSF-R.
Mutations of the granulocyte-colony stimulating factor receptor in patients with severe congenital neutropenia are not required for transformation to acute myeloid leukaemia and may be a bystander phenomenon.
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.
Here we describe the identification of a novel point mutation in the extracellular domain of the G-CSF receptor (G-CSF-R) in an SCN patient who failed to respond to G-CSF treatment.
In this study, we show that the Lyn and Syk kinases are associated with the G-CSFR in neutrophils from SCN patients with point mutations in the cytoplasmic domain of the G-CSFR mRNA.
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 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).
In contrast, mutations in the G-CSF receptor in CN are acquired and are most probably connected with progression of the neutropenia into MDS/leukemia as a result of a loss of differentiation signaling.
Time course of increasing numbers of mutations in the granulocyte colony-stimulating factor receptor gene in a patient with congenital neutropenia who developed leukemia.
A subgroup of patients with severe congenital neutropenia (SCN) has been shown to harbor mutations in the G-CSF receptor gene that resulted in the truncation of the receptor's carboxyl-terminal region.
Recent studies have shown that point mutations in granulocyte colony-stimulating factor receptor (G-CSFR) are involved in the pathogenesis of severe congenital neutropenia (SCN) and in the transformation of SCN to acute myelogenous leukemia (AML).