Interferon-α induces dendritic cell differentiation of CML mononuclear cells in vitro and in vivo

The ability of interferon-a (IFNI-a) to induce dendritic cell (DC) differentiation in chronic myeloid leukemia (CIVIL) was evaluated. Peripheral blood mononuclear cells from CIVIL patients cultured with IFN-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) developed a dendritic morphology. Fluorescence in situ hybridization demonstrated that the DCs harbored the bcr/ab/translocation. The DCs prepared with IFNalpha/GM-CSF expressed significantly higher levels of class I and II HLA than those grown in interleukin-4 (IL-4) and GM-CSF. The DCs prepared from newly diagnosed CML patients using IFNalpha/GM-CSF expressed immunoregulatory proteins at levels comparable to normal DCs. In contrast, DCs cultured from CML patients who did not achieve a cytogenetic response to IFN-alpha expressed significantly lower levels of class I FILA, CD40, CD54, CD80 and CD86 than normal DCs. The expression of CD86 by CIVIL DCs was enhanced when they were cultured with IFN-alpha/IL-4/GM-CSF, or when IFN-alpha/GM-CSF-treated cells were induced to mature by CD40 ligand. The DCs from IFN-alpha failures were less stimulatory than normal DCs in the allogeneic mixed leukocyte reaction. CIVIL patients who had a cytogenetic response to IFN-alpha initially had low numbers of bone marrow DCs that increased significantly with treatment, while nonresponders had more prevalent DCs at baseline that showed no consistent change with treatment. Therefore, IFN-alpha can induce DC differentiation from CIVIL progenitor cells both in vitro and in vivo. The therapeutic activity of IFN-alpha in CIVIL may be due to its ability to stimulate the generation of DCs that can present CIVIL-specific antigens. Resistance to IFN-alpha may result when DC differentiation becomes impaired.