Calcium signaling induces acquisition of dendritic cell characteristics inchronic myelogenous leukemia myeloid progenitor cells

Effective host T lymphocyte sensitization to malignant cells depends on suc cessful antigen presentation. In this study, me examined the capacity of ma lignant myeloid progenitor cells of patients in the chronic phase of chroni c myelogenous leukemia (CML) to acquire characteristics of activated dendri tic cells (DCs) after intracellular calcium mobilization, thereby bypassing a need for third-party antigen-presenting cells. Treatment of purified CD3 3(+) CML cells from 15 patients with calcium ionophore (CI) consistently re sulted in de novo expression of the costimulatory molecules CD80 (B7.1) and CD86 (B7.2), CD40 and the DC-specific activation marker CD83, as well as m arked up-regulation of MHC class I and II molecules and the adhesion molecu le CD54. Most of these changes occurred within 24 hr of treatment, Morpholo gically, CI-treated CML cells developed long dendritic projections similar to those seen in mature DCs, Functionally, CI-treated CML cells provided st imulation of allogeneic T lymphocytes 10- to 20-fold that of untreated CML cells or untreated monocytes, Fluorescent in situ hybridization of CI-activ ated CML cells confirmed their leukemic origin by displaying the typical bc r/abl fusion signal. No difference in bcr/abl translocation percentages bet ween untreated and CI-treated CML nuclei was observed. These observations i ndicate that calcium mobilization may constitute a valuable approach for ra pidly and reliably generating CML-derived DCs for immunotherapy of CML.