DOWN SYNDROME AND ACUTE LEUKAEMIA: INCREASED RISK MAY BE DUE TO TRISOMY 21

The increased risk of acute leukaemia in patients with DS who have a + 21 is directly related to the presence, in all cells of these individuals, of the same chromosome change that is commonly seen in the leukaemic cells of children with children with ALL, the type ofLeukaemia most commonlyseen in DS children.

Abstract

Individuals with Down syndrome (DS), especially children, have an increased incidence of acute leukaemia. It is suggested that this increased risk is specifically associated with the presence of an extra chromosome 21 (+ 21) as a constitutional abnormality. Data available from surveys of non-DS patients with acute lymphocytic leukaemia (ALL) and acute non-lymphocytic leukaemia (ANLL) indicate that a + 21 is the most common change in leukaemic cells in ALL, especially in children, and that it is one of the more common changes in ANLL. In neonatal patients with mosaicism for normal cells and + 21 cells who have a transient leukaemoid reaction, the blast cells involve the + 21 clone; spontaneous disappearance of the leukaemoid reaction parallels a decrease in + 21 cells in the bone marrow. Thus, the increased risk of acute leukaemia in patients with DS who have a + 21 is directly related to the presence, in all cells of these individuals, of the same chromosome change that is commonly seen in the leukaemic cells of children with ALL, the type of leukaemia most commonly seen in DS children. This observation is analogous to that for two other constitutional chromosome abnormalities that are associated with an increased risk of a malignant tumour. A deletion of chromosome 13, including band 13q14 is associated with retinoblastoma, and a deletion of chromosome 11, including band 11p13 is associated with aniridia/Wilms tumour syndrome. The nature of the genes affected by these various chromosome aberrations is unknown.