.Chronic myelogenous leukemia is a myeloproliferative disease that comprises about 15% of all newly-diagnosed cases of leukemia is the United States each year. Disease progression is due to the chimeric protein known as Bcr-Abl., a constitutively active tyrosine kinase. Bcr-Abl results from the the Philadelphia Chromosome, an oncogene formed by a reciprocal translocation between chromosomes 9 & 22. Bcr-Abl p210 is most commonly found in patients but a more aggressive form know as p190 has been found in patients with more severe cases. Work from our laboratory has produced a p190 phenocopy mutant known as S509A with a single-point mutation (serine to alanine) to further study active sites within the molecule. The Rho-GEF portion of Bcr-Abl harbors several functional domains that contribute to leukemogenesis. Marked differences in cytokine levels and resulting phenotypes were observed in each variant in our laboratory studies (p210, p190, and S509A). To study these variants, a murine myeloblastoid cell line was used as an in vitro model. Cells expressing one of each of the aforementioned Bcr-Abl variants underwent a cytokine array with additional assays which revealed that the cytokine IRF8 expression was maintained. IRF8 directly binds to Bcr-Abl at amino acid 104, is phosphorylated & acts as a transcripion factor to produce more of itself. This can rapidly alter normal myelpoiesis & allows granulocyte/macrophage progenitors to abberantly proliferate and then quickly undergo apoptosis. The dysregulation of IRF8 and rapid apoptosis of cells that could not fully mature, only to be replaced quickly with myeloblasts was observed in our work. This finding was important, as blast cells are typically found in plethoric numbers at the most aggressive & terminal phase of the disease known as blast crisis. Further research into the regulation of IRF8 in the context of CML is essential as it may provide new therapeutics