Impact of IL-6 pathway inhibition on TET2 mutant clonal expansion. (A) Experimental protocol for TCZ administration. All 3 CH macaques were given a weekly dose of 10 mg/kg TCZ IV for 4 months. (B) Summary table of the status of 3 macaques at the time of initiation of TCZ. (C) Indel frequencies at the DTA target sites in PB granulocytes before, during, and after TCZ administration were quantified via targeted deep sequencing. The black line and shading indicate the period of TCZ administration. (D) Heatmap of specific TET2 indels over time before and after TCZ administration in ZH63 granulocytes. (E) Percent changes in growth rate per month of expanding clones in all 3 animals prior to TCZ, during TCZ, and after TCZ in the 3 animals, including TET2 clones in all 3 animals and DNMT3A clones in ZL39. The time periods used for pre-TCZ growth rate calculations began with samples collected 6 to 9 months posttransplantation, when stabilization of long-term hematopoiesis occurs in transplanted macaques, and until the first dose of TCZ. Negative values correspond to shrinkage of edited clones.