Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN

Species-Specific Therapy of Acute Lymphoid Leukemia

Forty years ago, Farber and associates described temporary remissions of acute leukemia in children produced by folic acid antagonists [13]. This ignited the hope that this most frequent and always fatal childhood cancer might be curable by drugs. Twenty years ago, Aur and as-sociates completed accession of patients to total therapy study V, the first treat-ment protocol to result in 50 % cure of acute lymphoid leukemia (ALL) [3]. Their results stand 20 years later (Fig. 1), and have been reproduced throughout the world in many thousands of children [6]. More important, recent national vital statistics of the United States and the United Kingdom indicate a 50 % reduc-tion in childhood leukemia mortality [4, 29]. Further, the cured children generally enjoy a normal life-style without need for medication. In the past 20 years, efforts have been directed at improving the cure rate of ALL while simplifying curative treat-ment, reducing its side effects, and im-proving its availability and accessibility. In a Stohlman Lecture at Wilsede 10 years ago the following statement was made [32]:- The most significant opportunity for improving the treatment of acute lymphoid leukemia in the past five years has been its biological and clini-cal classification by immunological cell surface markers. This allows spe-cies identification of the leukemia cells, the first step toward developing specific cytocidal or cytostatic therapy