Findings shed light on how leukemia protein works

A fusion protein called AML1-ETO is known to play a causal role in about 15% of acute myeloid leukemia cases. Now, new research suggests that this protein promotes malignancy by silencing E protein transcription factors.

In a study reported in the August 27th issue of Science, Dr. Robert G. Roeder and colleagues, from The Rockefeller University in New York, show that by binding to E proteins, AML1-ETO prevents the recruitment of critical coactivators.This interaction means that the E protein complex may be unable to activate the transcription of certain tumor suppressor genes. As a result, this increases the odds that a malignant phenotype will be expressed. At this point, however, the actual genes targeted by E protein remain to be determined, the researchers note.”Our results lead to the hypothesis that there are E protein target genes whose dysregulation by AML1-ETO may be important for…leukemogenesis, and they set the stage for identification of these genes and for analyses of the structural basis of the underlying, newly defined regulatory factor interactions,” they add. (Source: Science 2004;305:1286-1289: Reuters Health News: Oncolink: August 2004.)