A NOVEL FUSION BETWEEN MOZ AND THE NUCLEAR RECEPTOR COACTIVATOR TIF2 IN ACUTE MYELOID-LEUKEMIA

Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of acute myeloid leukemia with French-American-British M4/5 mo rphology and prominent erythrophagocytosis by the blast cells. This su btype is usually associated with the t(8;16)(p11;p13), a translocation that has recently been shown to result in a fusion between the MOZ an d CBP genes. We have cloned the inv(8)(p11q13), an abnormality associa ted with the same leukemia phenotype, and found a novel fusion between MOZ and the nuclear receptor transcriptional coactivator TIF2/GRIP-1/ NCoA-2. This gene has not previously been implicated in the pathogenes is of leukemia or other malignancies. MOZ-TIF2 retains the histone ace tyltransferase homology domains of both proteins and also the CBP bind ing domain of TIF2, We speculate that the apparently identical leukemi a cell phenotype observed in cases with the t(8;16) and the inv(8) ari ses by recruitment of CBP by MOZ-TIF2, resulting in modulation of the transcriptional activity of target genes by a mechanism involving abno rmal histone acetylation, (C) 1998 by The American Society of Hematolo gy.