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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.

Submitted April 1, 2003
Accepted September 5, 2003
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 Foa, and Filippo Belardelli*
Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy
Department of Cellular Biotechnologies and Hematology, University 'La Sapienza', Rome, Italy
* Corresponding author; email: belard{at}iss.it.
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 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 LPS. Treatment of CML monocytes with IFN- and GM-CSF resulted in the rapid generation of activated DCs (CML-IFN-DCs), expressing IL-15 and the anti-apoptotic bcl-2 gene. These cells were fully competent to induce IFN- production by co-cultured 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: i) the generation of highly active monocyte-derived DCs could be important for the induction of an antitumor response in IFN-treated CML patients; ii) IFN- can represent a valuable cytokine for the rapid generation of active monocyte-derived DCs to be utilized for vaccination strategies of CML patients.

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