Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells.
Effective host T lymphocyte sensitization to malignant cells depends on successful antigen presentation. In this study, we examined the capacity of malignant myeloid progenitor cells of patients in the chronic phase of chronic myelogenous leukemia (CML) to acquire characteristics of activated dendritic cells (DCs) after intracellular calcium mobilization, thereby bypassing a need for third-party antigen-presenting cells. Treatment of purified CD33(+) CML cells from 15 patients with calcium ionophore (CI) consistently resulted 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 marked up-regulation of MHC class I and II molecules and the adhesion molecule CD54. Most of these changes occurred within 24 hr of treatment. Morphologically, CI-treated CML cells developed long dendritic projections similar to those seen in mature DCs. Functionally, CI-treated CML cells provided stimulation of allogeneic T lymphocytes 10- to 20-fold that of untreated CML cells or untreated monocytes. Fluorescent in situ hybridization of CI-activated CML cells confirmed their leukemic origin by displaying the typical bcr/abl fusion signal. No difference in bcr/abl translocation percentages between untreated and CI-treated CML nuclei was observed. These observations indicate that calcium mobilization may constitute a valuable approach for rapidly and reliably generating CML-derived DCs for immunotherapy of CML.
Engels
F H
FH
Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
Koski
G K
GK
Bedrosian
I
I
Xu
S
S
Luger
S
S
Nowell
P C
PC
Cohen
P A
PA
Czerniecki
B J
BJ
D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood*; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D002118:Calcium / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D003713:Dendritic Cells / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D063268:Sialic Acid Binding Ig-like Lectin 3; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D015815:Cell Adhesion Molecules; D063268:Sialic Acid Binding Ig-like Lectin 3; D002118:Calcium