title: Long-term follow-up of granulocyte colony-stimulating factor receptor mutations in patients with severe congenital neutropenia: implications for leukaemogenesis and therapy.
abstract: Severe congenital neutropenia (SCN) is characterized by profound neutropenia, recurrent severe bacterial infections and maturation arrest in the myeloid lineage. Granulocyte colony-stimulating factor (G-CSF) treatment results in clinical improvement in over 90% of cases. Point mutations of the G-CSF receptor (G-CSFR) have been implicated in the progression of SCN to acute myeloid leukaemia (AML). Data are presented here on the 9-year follow-up of seven patients and the further screening of 18 other cases. One of the two original cases with a G-CSFR mutation has improved clinically; nevertheless, mutant DNA could still be detected at a very low level > 8 years after identification. The second child with a mutation progressed to myelodysplasia/AML 5 years after her mutation was detected. No mutations were found in the 18 new cases. One of three transformed cases had a G-CSFR mutation. This work is in agreement with the suggestion that G-CSFR mutations may provide a survival advantage to haemopoietic stem cells, but argues against the inevitability of leukaemic progression in their presence. Furthermore, the low frequency of G-CSFR mutations in SCN and the importance of regular screening and close clinical and laboratory follow-up if a mutation is found were demonstrated.
authors.affiliation: Department of Haematology, University College London, London, UK. p.ancliff@ucl.ac.uk
authors.forename: Phil J
authors.initials: PJ
authors.lastname: Ancliff
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Gale
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.forename: Ian
authors.initials: I
authors.lastname: Hann
authors.forename: David C
authors.initials: DC
authors.lastname: Linch
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D009503:Neutropenia / Q000151:congenital / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor