Defining the role of G-coupled protein receptor Gpr56 in acute myeloid leukemia

The G-protein coupled receptor 56 (GPR56) was identified as part of the molecular signature of leukemic stem cells isolated from patients with acute myeloid leukemia (AML), but the oncogenic potential of Gpr56 is unknown. This thesis demonstrates high expression of Gpr56 in the more primitive hematopoietic cells with decreased expression upon differentiation. Retroviral overexpression and transplant of Gpr56 in normal hematopoietic cells was not oncogenic and did not interfere with normal hematopoiesis. Increased Gpr56 expression in the context of Hoxa9 long-term cultures increased the aggressiveness of the disease by reducing the disease latency. Engraftment of human primary patient sample was reduced in the bone marrow upon the addition of an anti-GPR56 antibody. In summary, these data demonstrate that high expression of GPR56 is able to contribute to Hoxa9 induced AML development and provides a potential novel target for antibody-mediated anti-leukemic strategies