Generation of Dendritic Cells from Leukaemia Cells of a Patient with Acute Promyelocytic Leukaemia by Culture with GM-CSF, IL-4 and TNF-α

Abstract

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-α 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.

C-fms expression correlates with monocytic differentiation in PML-RARα+ acute promyelocytic leukemia

“…It is of interest to note that recent studies [44][45][46] have provided evidence that APL blasts also possess the capacity to differentiate to functional dendritic cells. This finding is fully compatible with our observations and it is tempting to suggest that the APL blasts differentiating to dendritic cells under appropriate culture conditions (ie in the presence of GM-CSF, IL-4 and Leukemia TNF-␣), represent the same population able to mature to monocytic cells also under the culture conditions here reported.…”

Prevention of Murine Acute Graft-versus-Host Disease by Recipient-Derived Paired Immunoglobulin-Like Receptor B Lentivirus-Transfected Dendritic Cells

“…Myeloid DCs are versatile APCs, which are derived from monocytes and hematopoietic BM cells [1]. In peripheral tissues, imDCs endocytose antigen, process it into peptides to form MHC-peptide complexes and migrate to lymph nodes where they present antigen to T cells [11].…”

“…Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs) that induce and regulate immune reactivity [1]. Mature DCs can stimulate T cells through high expression of MHCII and costimulatory molecules (CMs), while immature DCs (imDCs) inhibit T-cell responses and induce tolerance.…”

Cytokines in the Differentiation Therapy of Leukemia: From Laboratory Investigations to Clinical Applications

“…179,180 In recent years, there has been an increasing interest in the induction of leukemic cell differentiation into the dendritic lineage for immunotherapeutic applications. 181,182 Induction of differentiation of acute and chronic myeloid leukemic blasts with various differentiation-inducing agents into the DC lineage has recently been developed as a strategy to prime the host immune system. 183 Similarly, treatment of monocytes from CML patients with IFN-α and GM-CSF resulted in the rapid generation of activated DCs.…”