Infantile leukemia and soybeans - a hypothesis

Recent molecular-genetic studies have revealed that in the majority of patients with secondary leukemia induced by topoisomerase II (topo II) inhibitors and also with infantile acute leukemia (IAL), the breakpoints are clustered within scaffold attachment regions (SARs) of 3'-MLL-bcr near exon 9. Genistein, abundant in soybeans, is reported to be a potent nonintercalative topo II inhibitor. It interferes with the break reseal reaction of topo It by stabilizing a cleavable complex, which in the presence of detergents, results in DNA strand breaks. The present study revealed that genistein induced chromatid-type aberrations, in which chromatid exchanges are often observed. Genistein seems to act in a manner very similar to that of VP-16, although the latter is reported to produce both chromatid- and chromosome-type aberrations. In view of this pharmacological similarity between genistein and VP-16, and also the similarity of breakpoint clustering regions within the MLL gene in reported cases with secondary leukemia and IAL, genistein may be largely responsible for the development of IAL.