HLA loss is sufficient for clonal expansion, but does not prevent clonal evolution. A schematic diagram of 3 types of clonal architecture found in patients with somatic HLA loss. (A) Four patients had oligoclonal hematopoiesis with multiple independent events of HLA loss, without other nonsynonymous or regulatory region somatic mutations. (B) One patient had HLA loss and somatic mutations occurring in independent clones, where the clone bearing MDS-associated mutations expanded to replace the clone with HLA loss. (C) Two patients were found to have oligoclonal hematopoiesis with clones missing HLA alleles occurring in the same cells as somatic mutations, which were either subclonal or co-occurred with HLA loss in all cells analyzed.