Generation of dendritic cells from leukaemia cells of a patient with acute promyelocytic leukaemia by culture with GM-CSF, IL-4 and TNF-alpha.
Dendritic cells are potent antigen-presenting cells derived from CD34+ haemopoietic stem cells. Dendritic cells have been reported to be generated from cells in granulocytic lineage as well as monocytes, blood dendritic cell precursors and lymphoid progenitors. In order to explore the differentiation pathway of dendritic cells from granulocytic cells and the applicability of leukaemia-derived dendritic cells for anti-leukaemic immunotherapy in acute leukaemia of granulocytic origin, we tried to generate dendritic cells from leukaemia cells of a patient with acute promyelocytic leukaemia (APL). Leukaemia cells were cultured with GM-CSF, IL-4 and TNF-alpha for 10 days. Azurophilic granule-containing cells with marked cytoplasmic projections were generated in the culture. FACS analysis of these cultured cells revealed the generation of CD1a+, CD83+, CD80+, CD86+, CD40+ and HLA-DR+ cells. The leukaemic origin of these dendritic-like cells was demonstrated by in situ hybridization of magnetic-bead-sorted CD1a+ dendritic cells using the DNA probes of t(15;17). Cells generated by culturing leukaemia cells were demonstrated to have a potent antigen-presenting function in allogeneic mixed leucocyte cultures. These findings show the plausibility of the previously reported pathway of dendritic cell maturation through granulocytic cells and suggest the possibility of anti-leukaemic immunotherapy using leukaemia-derived dendritic cells even in patients with acute promyelocytic leukaemia.
Narita
M
M
School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan. naritami@clg.niigata-u.ac.jp
Takahashi
M
M
Liu
A
A
Ayres
F
F
Satoh
N
N
Abe
T
T
Nikkuni
K
K
Furukawa
T
T
Toba
K
K
Aizawa
Y
Y
D000328:Adult; D017951:Antigen Presentation; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D002884:Chromosomes, Human, Pair 15 / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17 / Q000648:ultrastructure; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D018189:Immunomagnetic Separation; D016130:Immunophenotyping; D017403:In Situ Hybridization; D015847:Interleukin-4 / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D007959:Lymphocyte Culture Test, Mixed; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D014178:Translocation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor