DETECTION OF CBP REARRANGEMENTS IN ACUTE MYELOGENOUS LEUKEMIA WITH T(8-16)

The CREB-binding protein (CBP) is a large nuclear protein that regulat es many signal transduction pathways and is involved in chromatin-medi ated transcription. The translocation t(8;16)(p11;p13.3) consistently disrupts two genes: the CBP gene on chromosome band 16p13.3 and the MO Z gene on chromosome band 8p11. Although a fusion of these two genes a s a result of the translocation is expected, attempts at detecting the fusion transcript by reverse transcriptase polymerase chain reaction (RT-PCR) have proven difficult; to date, only one in-frame CBP/MOZ fus ion transcript has been reported. We therefore sought other reliable m eans of detecting CBP rearrangements. We applied fluorescence in situ hybridization (FISH) and Southern blot analyses to a series of AML pat ients with a t(8;16) and detected DNA rearrangements of both the CBP a nd the MOZ loci in all cases tested. All six cases examined for CBP re arrangements have breakpoints within a 13 kb breakpoint cluster region at the 5' end of the CBP gene. Additionally, we used a MOZ cDNA probe to construct a surrounding cosmid contig and detect DNA rearrangement s in three t(8;16) cases, all of which display rearrangements within a 6 kb genomic fragment of the MOZ gene. We have thus developed a serie s of cosmid probes that consistently detect the disruption of the CBP gene in t(8;16) patients. These clones could potentially be used to sc reen other cancer-associated or congenital translocations involving ch romosome band 16p13.3 as well.