Figure 2.

Illustrative example of an individual case with clonal hematopoiesis and myeloproliferative neoplasm (MPN) disease progression. Individuals without hematological diseases may have somatic mutations in genes that do not impact hematopoiesis (i.e., passenger mutations, indicated with pink dots). At some point, the individual case represented in this figure acquires a mutation (e.g., in DNMT3A) that causes clonal expansion of the hematopoietic stem cell (HSC) without necessarily causing an overt hematological disease (i.e., clonal hematopoiesis of indeterminate potential [CHIP]), indicated with blue dots and expansion of the blue clone from 10% to 30%. Subsequently, this individual acquires one of the MPN phenotypic “driver” mutations (e.g., JAK2^V617F, indicated with orange dots), that results in the development of an MPN (e.g., polycythemia vera [PV] or essential thrombocythemia [ET]). Chronic phase MPN (i.e., PV or ET) may then progress to secondary myelofibrosis (sMF) on acquisition of additional mutations (e.g., a mutation in EZH2 [indicated with green dots]). This clone expands over time and, finally, overt secondary acute myeloid leukemia (sAML) may arise on acquisition of a TP53 mutation (yellow dots).