Down-regulation of cellular vascular endothelial growth factor levels induces differentiation of leukemic cells to functional leukemic-dendritic cells in acute myeloid leukemia.
We examined the effect of cellular vascular endothelial growth factor (VEGF) levels on the generation of leukemic dendritic cells (DCs). Leukemic DCs were successfully generated in vitro from bone marrow cells of 16 of 21 acute myeloid leukemia (AML) patients, and the cellular VEGF concentrations in the leukemic cells and the neutralization of VEGF with anti-VEGF antibody were determined. AML cells that failed to generate leukemic DCs showed significantly higher cellular VEGF levels compared with generated leukemic DCs, and down-regulation of cellular VEGF levels induced the generation of leukemic DCs from AML cells. Inhibition of cellular VEGF levels increased interleukin (IL)-12 production and the allostimulatory capacity of leukemic DCs. These results suggest that the generation of leukemic DCs from AML cells is inversely related to the VEGF production of the cells and that the down-regulation of cellular VEGF levels can induce potential differentiation of leukemic cells to functional leukemic DCs in patients with AML.
Kang
Hyun-Kyu
HK
Department of Hematology-Oncology, Chonnam National University Medical School, Gwangju, Korea.
Park
Jung-Sun
JS
Kim
Sang-Ki
SK
Choi
Bo-Hwa
BH
Pham
Than-Nhan Nguyen
TN
Zhu
Xiao-Wei
XW
Cho
Duck
D
Nam
Jong-Hee
JH
Kim
Young-Jin
YJ
Rhee
Joon-Haeng
JH
Chung
Ik-Joo
IJ
Kim
Hyeoung-Joon
HJ
Lee
Je-Jung
JJ
D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D002469:Cell Separation; D003713:Dendritic Cells / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D042461:Vascular Endothelial Growth Factor A