CONSISTENT INTERGENIC SPLICING AND PRODUCTION OF MULTIPLE TRANSCRIPTSBETWEEN AML1 AT 21Q22 AND UNRELATED GENES AT 3Q26 IN (321)(Q26Q22) TRANSLOCATIONS

Two genes have been implicated in leukemias of patients with abnormali ties of chromosome 3, band q26: EVI1, which can be activated over long distances by chromosomal rearrangements involving 3q26, and EAP, a ri bosomal gene that fuses with AML1 in a therapy-related myelodysplasia patient with a t(3;21)(q26.2;q22). AML1 was identified by its involvem ent in the t(8;21)(q22;q22) of acute myeloid leukemia. Here we report the consistent identification of fusion transcripts between AML1 and E AP or between AML1 and previously unidentified sequences that we named MDS1 (MDS-associated sequences) in the leukemic cells of four patient s with therapy-related myelodysplasia/acute myeloid leukemia and in on e patient with chronic myelogenous leukemia in blast crisis, all of wh om had a t(3;21). In addition, we have identified a third chimeric tra nscript, AML1/EVI1, in one of the therapy-related acute myeloid leukem ia patients. Pulsed-field gel electrophoresis established the order of the genes as EAP, the most telomeric, and EVI1, the most centromeric, gene. The results indicate that translocations could involve multiple genes and affect gene expression over long distances.