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Mutations of the granulocyte‐colony stimulating factor receptor in patients with severe congenital neutropenia are not required for transformation to acute myeloid leukaemia and may be a bystander phenomenon
Author(s) -
Bernard Tanya,
Gale Rosemary E.,
Evans Jane P. M.,
Linch David C.
Publication year - 1998
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.1365-2141.1998.00652.x
Subject(s) - congenital neutropenia , immunology , neutropenia , myeloid , mutation , granulocyte colony stimulating factor receptor , biology , granulocyte colony stimulating factor , haematopoiesis , point mutation , cancer research , medicine , gene , genetics , chemotherapy , stem cell
Point mutations of the granulocyte‐colony stimulating factor receptor (G‐CSFR) resulting in an abnormally truncated receptor have been implicated in the pathogenesis of some cases of severe congenital neutropenia (SCN) and in the transformation of SCN to acute myeloid leukaemia (AML). We report here studies in 11 patients with SCN. No mutations were detected in the one patient who developed AML indicating that development of such mutations is not a prerequisite for transformation. Truncation mutations were detected in a minor percentage of transcripts from two other patients. In one patient the mutation has been constant at a low level (5–10% of total mRNA and 2/40 myeloid colonies) for 2 years. In the other patient the mutation was acquired, remained present at low levels for nearly 3 years and then spontaneously disappeared. Both patients had polyclonal haemopoiesis. We hypothesize that these mutations do not cause SCN, are randomly acquired with the mutant clone being expanded to detectable levels by high levels of exogenous or endogenous G‐CSF, and may disappear by clonal succession. In a pre‐leukaemic marrow the mutated subclone could achieve high levels, but this does not necessarily indicate a primary role of the mutant receptor in the leukaemogenic process.