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

被引:43
作者
Bernard, T
Gale, RE
Evans, JPM
Linch, DC
机构
[1] UCL, Sch Med, Dept Haematol, London WC1E 6HX, England
[2] Great Ormond St Hosp Sick Children, Dept Haematol, London WC1N 3JH, England
基金
英国惠康基金;
关键词
severe congenital neutropenia; G-CSF receptor mutations; AML;
D O I
10.1046/j.1365-2141.1998.00652.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 le-cds 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.
引用
收藏
页码:141 / 149
页数:9
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