Immunomodulatory kits generating leukaemia derived dendritic cells do not induce blast proliferation ex vivo: IPO-38 as a novel marker to quantify proliferating blasts in acute myeloid leukaemia

Abstract

(Leukaemia derived) dendritic cells (DC, DC_leu) are potent stimulators of anti-leukaemic activity in acute myeloid leukaemia (AML) and can be generated with immunomodulatory kits containing granulocyte-macrophage-colony-stimulating-factor (GM-CSF), prostaglandin-E₁ (PGE₁), prostaglandin-E₂ (PGE₂) and/or picibanil (OK-321). Potential adverse effects initiated through kits, especially the proliferation of blasts, must be ruled out to ensure treatment safety. We quantified proliferating blasts with the proliferation markers CD71 and Ki-67 and the novel proliferation marker IPO-38 before and after kit treatment ex vivo. IPO-38 hereby appeared to be the most sensitive marker; a combination with CD71 may add value when assessing proliferation kinetics. Kit treatment did not or only slightly (<5%) induce blast proliferation in most cases. An induction of blast proliferation was only found in single cases and could be compensated by DC_leu-induced anti-leukaemic activity in most times. Overall, we appraise kit treatment to be safe in vivo.

Keywords: Acute myeloid leukaemia; Anti-leukaemic functionality; Blast proliferation; IPO-38; Leukaemia derived dendritic cells; Proliferation marker.