AbstractChronic myelogenous leukemia (CML) is a malignant myeloproliferative disease arising from the clonal expansion of a stem cell expressing the bcr/abl oncogene. CML patients frequently respond to treatment with interferon-α (IFN-α), even though the mechanisms of the response remain unclear. In the present study, we evaluated the role of IFN-α in differentiation and activity of monocyte-derived dendritic cells (DCs) from CML patients as well as in modulation of the cell response to lipopolysaccharide (LPS). Treatment of CML monocytes with IFN-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in the rapid generation of activated DCs (CML-IFN-DCs) expressing interleukin-15 (IL-15) and the antiapoptotic bcl-2 gene. These cells were fully competent to induce IFN-γ production by cocultured autologous T lymphocytes and expansion of CD8+ T cells. LPS treatment of CML-IFN-DCs, but not of immature DCs generated in the presence of IL-4/GM-CSF, induced the generation of CD8+ T cells reactive against autologous leukemic CD34+ cells. Altogether, these results suggest that (1) the generation of highly active monocyte-derived DCs could be important for the induction of an antitumor response in IFN-treated CML patients and (2) IFN-α can represent a valuable cytokine for the rapid generation of active monocyte-derived DCs to be utilized for vaccination strategies of CML patients. (Blood. 2004;103:980-987)