THE TRANSLOCATION T(8-L6)(P11, P13) OF ACUTE MYELOID-LEUKEMIA FUSES APUTATIVE ACETYLTRANSFERASE TO THE CREB BINDING-PROTEIN

The recurrent translocation t(8;16)(p11;p13) is a cytogenetic hallmark for the M4/M5 subtype of acute myeloid leukaemia. Here we identify th e breakpoint-associated genes. Positional cloning on chromosome 16 imp licates the CREB-binding protein (CBP), a transcriptional adaptor/coac tivator protein. At the chromosome 8 breakpoint we identify a novel ge ne, MOZ, which encodes a 2,004-amino-acid protein characterized by two C4HC3 zinc fingers and a single C2HC zinc finger in conjunction with a putative acetyltransferase signature. In-frame MOZ-CBP fusion transc ripts combine the MOZ finger motifs and putative acetyltransferase dom ain with a largely intact CBP. We suggest that MOZ may represent a chr omatin-associated acetyltransferase, and raise the possibility that a dominant MOZ-CBP fusion protein could mediate leukaemogenesis via aber rant chromatin acetylation.