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Blood, 1 February 2004, Vol. 103, No. 3, pp. 980-987.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-03-0981.
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IMMUNOBIOLOGY
IFN- promotes the rapid differentiation of monocytes from patients with chronic myeloid leukemia into activated dendritic cells tuned to undergo full maturation after LPS treatment
Lucia Gabriele,
Paola Borghi,
Carmela Rozera,
Paola Sestili,
Mauro Andreotti,
Anna Guarini,
Enrico Montefusco,
Robert Foà, and
Filippo Belardelli
From the Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy; and Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy.
Chronic 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- (IFN- ), even though the mechanisms of the response remain unclear. In the present study, we evaluated the role of IFN- 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- 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- 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- 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)

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