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A point mutation in the granulocyte colony-stimulating factor receptor (G-CSF-R) gene in a case of acute myeloid leukemia results in the overexpression of a novel G-CSF-R isoform.
- Source :
-
Blood [Blood] 1995 Feb 15; Vol. 85 (4), pp. 902-11. - Publication Year :
- 1995
-
Abstract
- A novel human granulocyte colony-stimulating factor (G-CSF) receptor isoform, designated SD, has been identified in which the distal C-terminal cytoplasmic region, previously shown to be essential for maturation signalling, is substituted by an altered C-terminus. The SD receptor has a high affinity for G-CSF and retains the membrane-proximal cytoplasmic region known to be sufficient for proliferative signalling. Nonetheless, the SD isoform lacks the ability to transduce growth signals in murine BAF3 cells and, in contrast to the wild-type G-CSF receptor, is scarcely capable of activating JAK2 kinase. Expression of SD receptor was found to be low in normal granulocytes, but was significantly increased in a patient with acute myeloid leukemia (AML). The leukemic cells of this patient harbour a point mutation in the SD splice donor site of the G-CSF receptor gene. These findings provide the first evidence that mutations in the G-CSF receptor gene can occur in certain cases of clinical de novo AML. The possible contribution of defective G-CSF receptor signalling to leukemogenesis is discussed.
- Subjects :
- Acute Disease
Amino Acid Sequence
Animals
Base Sequence
Bone Marrow pathology
Bone Marrow Cells
Cell Division drug effects
Cell Line
DNA biosynthesis
DNA Primers
Gene Expression
Gene Expression Regulation, Neoplastic
Granulocyte Colony-Stimulating Factor metabolism
Granulocyte Colony-Stimulating Factor pharmacology
Kinetics
Leukemia, Myeloid blood
Leukemia, Myeloid pathology
Mice
Molecular Sequence Data
Polymerase Chain Reaction
Protein Kinases metabolism
Receptors, Granulocyte Colony-Stimulating Factor metabolism
Reference Values
Transfection
Leukemia, Myeloid genetics
Point Mutation
Receptors, Granulocyte Colony-Stimulating Factor biosynthesis
Receptors, Granulocyte Colony-Stimulating Factor genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 85
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 7531515