DETECTION AND SUBCELLULAR-LOCALIZATION OF AN AML1 CHIMERIC PROTEIN INTHE T(8-21) POSITIVE ACUTE MYELOID-LEUKEMIA

AML1, a gene encoding a protein of the PEBP2/CBF family of transcripti on factors is disrupted by translocations associated with human leukem ia. In the t(8;21) acute myelogenous leukemia (AML), AML1 was found fu sed to a gene on chromosome 8 that we designated CDR (also known as ET O and MTG8). Immunoprecipitation experiments followed by immunoblottin g using a combination of antibodies against different epitopes of one of the predicted chimeric proteins encoded by a fully characterized fu sion transcript enabled us to visualize a chimeric protein in the t(8; 21) Kasumi-1 cell line. The estimated size of this protein is 64 kDa, Immunoblotting of leukemic blasts containing the t(8;21) detected a pr otein of the same size, Immunofluorescence experiments indicate that t he chimeric protein is localized in the nucleus. A normal AML1 protein of 27 kDa was also detected in t(8;21) Kasumi-1 cells, It remains to be established by which mechanism the mutant AML1 isoform may contribu te to the leukemogenesis process of t(8;21)-positive acute myeloid leu kemia.