Cytokine‐Driven Differentiation of Blasts from Patients with Acute Myelogenous and Lymphoblastic Leukemia into Dendritic Cells

Abstract

We investigated the ability of both acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) blasts to differentiate into dendritic cells (DC) in vitro.Cytokine-supplemented suspension cultures of leukemic blasts in 98 patients with AML and five patients with ALL (normal karyotype, n = 2; BCR/ABL, n = 3) were performed. Mononuclear cells out of peripheral blood or bone marrow containing between 60% and 90% leukemic blasts were cultured for eight days using different growth factor combinations.The highest yield of CD1a Leukemic DC can be generated out of leukemic progenitors in patients with AML. These cells might become relevant for autologous and allogeneic immunotherapy in selected patients. BCR/ABL-positive lymphoblasts could not be transformed into cells with an early dendritic phenotype with the cytokines used in our experiments.

Transduction of acute myeloid leukemia cells with third generation self-inactivating lentiviral vectors expressing CD80 and GM-CSF: effects on proliferation, differentiation, and stimulation of allogeneic and autologous anti-leukemia immune responses

“…21 In particular, since GM-CSF and interleukin-4 (IL-4) are key in obtaining monocytederived DC cultures in vitro, 22 the strategy to drive AML cells into DC differentiation ('AML-DC') in the presence of recombinant GM-CSF and IL-4 has been studied with variable but overall successful results. [23][24][25][26] It has been shown previously that autocrine stimulation after retroviral vector gene transfer of GM-CSF into multipotent murine stem cell lines (FDCP mix) induced their synchronous maturation, driving differentiation into granulocytes and macrophages. 27 To our knowledge, however, this is the first demonstration of a maturation effect in primary human AML cells after GM-CSF gene transfer.…”

An optimised biphasic culture system for the generation of functional dendritic cells from patients with acute lymphoblastic leukaemia at presentation and in clinical remission

“…Robinson et al 9 generated DC with allostimulatory capacity, using IL-4 + SCF, from four patients with bi-phenotypic leukaemia and Cignetti et al 21 used IL-4 + CD40L to culture DC from two ALL patients. In contrast, Kohler et al 22 were unsuccessful in attempts to generate DC from three patients with Ph + ALL using a number of cytokine combinations. Alternative strategies to generate CTL against ALL cells, using CD40L, have been reported.…”

Leukemic dendritic cells: potential for therapy and insights towards immune escape by leukemic blasts

“…119 Similar findings have since been reported by other investigators. [120][121][122][123][124][125][126][127][128][129][130][131][132] The high number of efficient co-stimulatory, adhesion and MHC molecules present on the membrane of these leukemic DCs could allow recruitment and activation of the rare specific anti-tumoral T cells that are supposed to belong to the naive lymphocyte pool. Moreover, to overcome the absence of identified leukemia-associated antigens, in the case of leukemic DCs, tumor cells themselves are used as immunogens.…”