title: 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.
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.
authors.affiliation: Department of Hematology, Dr. Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Dong
authors.forename: M
authors.initials: M
authors.lastname: van Paassen
authors.forename: C
authors.initials: C
authors.lastname: van Buitenen
authors.forename: L H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: B
authors.initials: B
authors.lastname: Löwenberg
authors.forename: I P
authors.initials: IP
authors.lastname: Touw
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D017931:DNA Primers; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000097:blood / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D012016:Reference Values; D014162:Transfection
chemical_list: D017931:DNA Primers; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D004247:DNA; D011494:Protein Kinases