Engagement of SIRPa Inhibits Growth and Induces Programmed Cell Death in Acute Myeloid Leukemia Cells

Background: Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRPa) on macrophages. Although AML cells express SIRPa, its function has not been investigated in these cells. In this study we aimed to determine the role of the SIRPa in acute myeloid leukemia. Design and Methods: We analyzed the expression of SIRPa, both on mRNA and protein level in AML patients and we further investigated whether the expression of SIRPa on two low SIRPa expressing AML cell lines could be upregulated upon differentiation of the cells. We determined the effect of chimeric SIRPa expression on tumor cell growth and programmed cell death by its triggering with an agonistic antibody in these cells. Moreover, we examined the efficacy of agonistic antibody in combination with established antileukemic drugs. Results: By microarray analysis of an extensive cohort of primary AML samples, we demonstrated that SIRPa is differentiall