The in-vitro generation of dendritic cells from blast cells in acute leukaemia

Dendritic cells (DC) are potent antigen-presenting cells responsible for th e initiation of primary antigen-specific immune responses. In chronic myelo id leukaemia DC have been generated from Ph+ cells and these Ph+ DC are cap able of stimulating cytolytic T-cell responses against the parent leukaemia cells. The prevalence of this phenomenon in acute leukaemia (AL) is unknow n and we have therefore studied a variety of acute leukaemias to determine their potential for DC development. Peripheral blood mononuclear cells (PBM C) from 21 cases of AL were cultured in GM-CSF + TNF alpha. Of these cases, 15 were viable in culture and cells with typical DC morphology were observ ed in 12 of these 15 cases. DC growing in culture expressed either CD1a and /or CD83 and were HLA-DR+ CD40(+) CD80(+) CD86(+) typical of mature DC. In 9/12 cases the cultured cells possessed potent antigen-presenting capacity as measured in the allo-MLR. The malignant origin of the cultured DC was co nfirmed by FISH analysis in two cases (one 5q- and one Ph+ AL) and by persi stent aberrant expression of CD19 in two cases of biphenotypic leukaemia. F unctional DC may be derived from AL blasts in a significant number of patie nts and such DC may be capable of inducing leukaemia-specific immune respon ses with potential for clinically beneficial effects.