2 - Down syndrome and chromosome 21 abnormalities in leukaemia

Abstract

Numerical and structural chromosome 21 abnormalities are associated with specific haematological neoplasms (Mitelman, 1988; Sandberg, 1990), thus suggesting the involvement of one or more genes on chromosome 21 in the control of cell growth and differentiation. The first indirect hint of an association between chromosome 21 and leukaemia comes from epidemiological data, showing that the relative risk of leukaemia in children with trisomy 21 and Down syndrome is 10-20 times higher than that of normal children (Fong and Brodeur, 1987; Zipursky et aI, 1987). The observation that trisomy 21cells are the ones involved in the leukaemic transformation in Down syndrome mosaics, and the observation that trisomy 21 is also common in acute lymphocytic (ALL) and myelogenous (AML) leukaemias in non-Down individuals made Rowley (1981) suggest an aetiological role for trisomy 21 in leukaemogenesis. However, acute leukaemia has also been reported in individuals with monosomy of the 21q22 region due to the germ-line inheritance of a ring chromosome 21. A few specificchromosome abnormalities involving chromosome 21 are also consistently associated with AML occurring in both children and adults. The most common is the t(8;21)(q22;q22) in AML with undifferentiated phenotype (Rowley, 1973). The situations in which chromosome 21 is involved are apparently diverse. Our current knowledge of the structure and genetic content of chromosome 21, as well as the recognition that genetic and cellular mechanisms such as genome imprinting and protein-protein interactions are also involved in producing cancer, may help us to unravel the molecular basis of leukaemias involving the smallest human autosome.