In HLA-matched HCT, alloreactive donor T cells recognize patient-specific MiHA peptides presented by HLA-A, -B, or -C molecules, via their T-cell receptor (TCR). (A) Hematopoietic MiHAs (red dots) are expressed selectively on hematopoietic tissues including their neoplastic derivatives (green cells), but not or to a much lesser extent on GVHD target tissues. Recognition of patient-specific hematopoietic MiHAs by alloreactive donor T cells after transplantation can lead to GVL (ie, control of the malignant disease) without GVHD (ie, T-cell-mediated damage to healthy tissues). Donor T-cell recognition of patient-specific hematopoietic MiHAs will not be harmful to the donor’s blood system reconstituted after successful HCT, because it carries the donor-specific variant of the relevant MiHA. The work by Fuchs et al added 11 new hematopoietic MiHAs to the 11 previously known ones, for a total number of 14. These hematopoietic MiHAs hold promise for new strategies of targeted leukemia immunotherapy. (B) Preferentially nonhematopoietic MiHAs (green dots) are broadly expressed on different tissues including GVHD target organs (light brown cells), in addition to varying levels of expression in hematopoietic tissues and their malignant derivatives (green cells). Recognition of patient-specific preferentially nonhematopoietic MiHAs by alloreactive donor T cells after transplantation can lead to both toxic GVHD and beneficial GVL. The study by Fuchs et al added 70 new preferentially nonhematopoietic MiHAs to the 75 previously known ones, for a total number of 145. Together, the 14 hematopoietic and 145 preferentially nonhematopoietic MiHAs cover most of the MiHA repertoire presented by several common HLA allotypes and provide an invaluable benchmark for the assessment of MiHAs as biomarkers for HCT outcome. Professional illustration by Patrick Lane, ScEYEnce Studios.