The biological characteristics of dendritic cells derived in vitro from myelogeneous leukemia cells and healthy donor cells.
Successful adoptive immunotherapy for leukemia depends on the generation of T cells that can specifically react with malignant cells. Dendritic cells (DCs) are important antigen-presenting cells in the development of antileukemia T-cell responses. Mononuclear cells (MNC) were isolated from peripheral blood or bone marrow of patients with chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML). After incubation with granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4, and tumor necrosis factor-alpha, MNC developed morphological characteristics of DCs in vitro, which were confirmed by phenotypic assay. Fluorescence in situ hybridization demonstrated the presence of fusion gene in the nuclei of representative CML or AML-M3 samples, indicating that the cells were leukemic in origin. IL-12 levels were significantly higher in AML-DCs and CML-DCs prestimulated with phorbol 12-myristate 13-acetate than in the corresponding leukemic cells, but were lower than that of healthy donors. These cells were potent stimulators of lymphocyte proliferation in specific in vitro assays for DC function. However, the stimulatory abilities of allogeneic T cells in a mixed lymphocyte reaction were impaired compared with those of mature DCs derived from healthy donors, although T-cell stimulatory effects were significantly increased in these differentiated leukemia-DCs. These results suggest that functional DCs may be derived from leukemic (AML, CML) blasts in a significant number of patients and may be capable of inducing leukemia-specific immune responses with potentially clinically beneficial effects.
Tong
X M
XM
Institute of Hematologic Disease, Department of Hematology, First Affliated Hospital, Medical School, Zhejiang University, Hangzhou, China.
Yao
H P
HP
Qian
W B
WB
Zhu
L F
LF
Fu
Z H
ZH
Huang
Z L
ZL
Jin
J
J
D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D007959:Lymphocyte Culture Test, Mixed