Beneficial effect of 6-mercaptopurine on the mitotic index of trisomy 21 lymphocytes. Implications for future research.

Low doses of 6-mercaptopurine were found to significantly increase the mitotic index in lymphocytes of patients with trisomy 21. This finding implies that excess purine synthesis in Down syndrome is responsible for lymphocyte cytotoxicity. We suggest that, in addition to the three steps already known, other genes involved in the "de novo" purine synthesis pathway might be located on chromosome 21 and that they are responsible for increased adenine nucleotides, nucleotide pool imbalance and perhaps relative guanine nucleotide deficiency. This would open new areas of research into the patho-physiology of trisomy 21.