Leukemia Research 30 (2006) 785–794 Circulating myeloid dendritic cell directly isolated from patients with chronic myelogenous leukemia are functional and carry the bcr-abl translocation Enrica Orsini ∗ , Elisabetta Calabrese, Roberta Maggio, Alessia Pasquale, Mauro Nanni, Stefania Trasarti, Agostino Tafuri, Anna Guarini, Robert Foa Dipartimento di Biotecnologie Cellulari ed Ematologia, University “La Sapienza”, Via Benevento 6, 00161 Rome, Italy Received 3 March 2005; accepted 22 May 2005 Available online 9 March 2006 Abstract Leukemic bcr-abl positive dendritic cells (DCs) are likely to be present in vivo in chronic myelogenous leukemia (CML) patients, but no data are available on their functional qualities. We analyzed the circulating BDCA-1+ myeloid DC compartment in 15 chronic phase CML patients. Phenotypic features of CML DCs were comparable with that of normal DCs, except for the CD80 and CD40 antigens, significantly under-represented in CML patients. Nonetheless, no differences were found between normal samples and leukemic DCs in the allostimulatory ability, as well as in the production of cytokines and polarization of T cell responses. CML DCs were analyzed by fluorescence in situ hybridization (FISH) and found positive for the bcr-abl translocation. However, when bcr-abl+ DCs were tested for their ability to stimulate an autologous T-cell response in vitro, we could not detect a specific recognition. We conclude that an apparently normal circulating DC compartment carrying the Ph+ chromosome can be identified in CML patients; however, these cells appear unable to trigger a protective anti-leukemic immune response in autologous T cells. © 2005 Elsevier Ltd. All rights reserved. Keywords: Dendritic cells; Chronic myelogenous leukemia; Bcr-abl; T cells; Costimulatory molecules 1. Introduction Chronic myelogenous leukemia (CML) represents a crit- ical model in hematology because is the first hematological malignancy in which a specific, pathogenetic and ubiqui- tous genetic marker has been identified [1–4]. The bcr-abl translocation is responsible for the malignant phenotype of leukemic cells in CML [5,6] and its product, the p210 fusion protein, also represents an example of tumor-specific antigen (Ag) [7–9]. For this reason, the possibility of exploiting the anti-brc-abl immune response in the treatment of CML, in particular in the chronic phase of the disease, before blas- tic evolution, has been intensely investigated. Phase I and II clinical trials have been performed, aimed at eliciting an ∗ Corresponding author. Tel.: +39 06 85795753; fax: +39 06 85795792. E-mail address: orsini@bce.uniroma1.it (E. Orsini). anti-leukemic specific T-cell immune response using bcr-abl- based vaccines [10–13]. Although a few clinical responses have been recorded in these studies, multiple evidences of immunologic activation and in vivo specific responses have been obtained, encouraging further studies in this direction. Dendritic cells (DC) are one of the most promising nat- ural adjuvant for the design of anti-tumor vaccines, given their unique abilities in the initiation and control of T-cell- mediated immune responses [14–16]. DC-based vaccines have been tested in different cancer diseases, including hema- tological malignancies, showing a good capability of eliciting specific responses [17]. In CML patients, the majority of in vitro monocyte-derived DCs are positive for the chimeric bcr-abl fusion gene [18,19], demonstrating their origin from the leukemic hematopoietic precursor. Therefore, an alterna- tive strategy for the design of tumor vaccines, in addition to priming T cells with DCs pulsed with CML antigens, can be 0145-2126/$ – see front matter © 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.leukres.2005.11.028