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Long‐term follow‐up of granulocyte colony‐stimulating factor receptor mutations in patients with severe congenital neutropenia: implications for leukaemogenesis and therapy
Author(s) -
Ancliff Phil J.,
Gale Rosemary E.,
Liesner Ri,
Hann Ian,
Linch David C.
Publication year - 2003
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2003.04160.x
Subject(s) - congenital neutropenia , neutropenia , granulocyte colony stimulating factor , mutation , granulocyte colony stimulating factor receptor , medicine , myeloid , immunology , granulocyte , myeloid leukemia , cancer research , chemotherapy , biology , genetics , gene
Summary. 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.