Preleukemic cells in CML and clonal hematopoiesis after TKI therapy. A hematopoietic stem and progenitor cell acquires a gene mutation or mutations and clonally expands (ie, becomes a preleukemia clone). A preleukemia cell gains a Ph chromosome and expands, and clinical CML develops. After treatment with a TKI, Ph⁺ cells are eradicated, and residual mutant Ph⁻ preleukemic cells expand and contribute to clonal hematopoiesis.