Identification of a nonsense mutation in the granulocyte-colony-stimulating factor receptor in severe congenital neutropenia
- Dr. Daniel den Hoed Cancer Center, Rotterdam (Netherlands)
- Erasmus Univ., Rotterdam (Netherlands)
- Free Univ., Amsterdam (Netherlands)
Severe congenital neutropenia (Kostmann syndrome) is characterized by profound absolute neutropenia and a maturation arrest of marrow progenitor cells at the promyelocyte-myelocyte stage. Marrow cells from such patients frequently display a reduced responsiveness to granulocyte-colony-stimulating factor (G-CSF). G-CSF binds to and activates a specific receptor which transduces signals critical for the proliferation and maturation of granulocytic progenitor cells. Here the authors report the identification of a somatic point mutation in one allele of the G-CSF receptor gene in a patient with severe congenital neutropenia. The mutation results in a cytoplasmic truncation of the receptor. When expressed in murine myeloid cells, the mutant receptor transduced a strong growth signal but, in contrast to the wild-type G-CSF receptor, was defective in maturation induction. This mutant receptor chain may act in a dominant negative manner to block granulocytic maturation. 40 refs., figs., 2 tabs.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 50646
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, Issue 10; Other Information: PBD: 10 May 1994
- Country of Publication:
- United States
- Language:
- English
Similar Records
Influence of histamine of precursors of granulocytic leukocytes in murine bone marrow
Myeloid cell kinetics in mice treated with recombinant interleukin-3, granulocyte colony-stimulating factor (CSF), or granulocyte-macrophage CSF in vivo