THE 3-21 TRANSLOCATION IN MYELODYSPLASIA RESULTS IN A FUSION TRANSCRIPT BETWEEN THE AML1 GENE AND THE GENE FOR EAP, A HIGHLY CONSERVED PROTEIN ASSOCIATED WITH THE EPSTEIN-BARR-VIRUS SMALL RNA EBER-1

In the 8;21 translocation, the AML1 gene, located at chromosome band 2 1q22, is translocated to chromosome 8 (q22), where it is fused to the ETO gene and transcribed as a chimeric gene. AML1 is the human homolog of the recently cloned mouse gene pebp2alphaB, homologous to the DNA binding a subunit of the polyoma enhancer factor pebp2. AML1 is also i nvolved in a translocation with chromosome 3 that is seen in patients with therapy-related acute myeloid leukemia and myelodysplastic syndro me and in chronic myelogenous leukemia in blast crisis. We have isolat ed a fusion cDNA clone from a t(3;21) library derived from a patient w ith therapy-related myelodysplastic syndrome; this clone contains sequ ences from AML1 and from EAP, which we have now localized to band 3q26 . EAP has previously been characterized as a highly expressed small nu clear protein of 128 residues (EBER 1) associated with Epstein-Barr vi rus small RNA. The fusion clone contains the DNA binding 5' part of AM L1 that is fused to ETO in the t(8;21) and, in addition, at least one other exon. The translocation replaces the last nine codons of AML1 wi th the last 96 codons of EAP. The fusion does not maintain the correct reading frame of EAP and may not lead to a functional chimeric protei n.