HHLA2 and acute myeloid leukemia: Since the role of TMIGD2 in AML is independent of engagement with its known ligand HHLA2 (Figs. 1d, 2d, g, h, and 7e, and Supplementary Fig. 7f), we hypothesized that TMIGD2 signaling in AML is triggered by: (1) a new binding partner; (2) a gain-of-function mutation; (3) trans- and/or cis-homophilic dimerization.