AML: Exposed and exploited?

Abstract

In this issue of Blood, Gillissen and colleagues characterize donor-derived cytotoxic antibodies, isolated from allogeneic hematopoietic cell transplant (HSCT) patients with acute myelogenous leukemia (AML) in sustained remission, that targeted the spliceosome U5 snRNP200 complex expressed on the cell membrane of AML blasts. Mechanistically, in vitro antibodydependent cytotoxicity did not cause leukemia cell apoptosis, but rather destabilization of the cell membrane cytoskeleton and subsequent pore formation, resulting in cellular swelling and extravasation of intracellular contents (oncosis). In addition, in vivo reduction in AML burden using a U5 snRNP200-specific antibody was demonstrated in a murine SCID xenograft model. Collectively, the authors' work suggests a potential role for donorderived antibodies in mediating graft-versus-leukemia (GVL) activity following allogeneic HSCT.