Age-related dichotomy of clonal hematopoiesis in aAA, manifested as frequent HLA loss in younger patients and as MDS-associated somatic mutations in older patients. A bubble scatter plot of somatic mutation analysis of the 17 patients with 1 of the 4 HLA risk alleles (HLA-A*33:03, HLA-A*68:01, HLA-B*14:02, or HLA-B*40:02); each patient is represented by a circle. The number of somatic nonsynonymous coding and regulatory region mutations identified by comparative WES is plotted on the y-axis, with the corresponding patient’s age at aAA diagnosis plotted on the x-axis; duration of disease at sequencing is depicted as the area of each point. PNH clones are not shown. Patients with HLA loss, as determined by the presence of either 6p CN-LOH or inactivating mutations in HLA alleles, are shown in blue. Patients with MDS-associated somatic mutations are shown in red. One patient had a transient clone of whole chromosome 6 CN-LOH early in disease course (blue circle accompanied by curved black arrow at the bottom right), which disappeared and was replaced by a dominant clone with MDS-associated mutations (red circle, indicated by a curved black arrow at the bottom right). HLA risk alleles are indicated next to each of the points; A, HLA-A; B, HLA-B.