Model of DNMT3A and TET2 clonal origin in CHIP.DNMT3A and TET2 mutations have different lineage involvement. This is compatible with DNMT3A mutations occurring in a multipotent HSC and TET2 mutations in a more committed HSC. Alternatively, DNMT3A and TET2 mutations may occur in a multipotent HSC, but lineage-specific proliferation is influenced by different intrinsic/extrinsic factors conferring a strong myeloid bias for TET2-mutated HSCs.