Fig. 5

Occurrence and manifestations of myelodysplastic hematopoiesis. MDS develops from the growth and propagation of a clone with somatic mutations of hematopoietic cells and generally evolves into AML. The characteristics and clinical manifestations vary in different phases. First, an initial mutation occurs in HSC, and additional mutations that pertain to clonal progression occur in progenitor or precursor cells, collectively forming a local clone. Next, as time elapses, mutant stem cells migrate and dwell within other BM regions (e.g., sternum, femur, and ilium) through peripheral blood to form local clones, and the condition is defined as the clonal hematopoiesis of indeterminate potential (CHIP) phase when hematopoietic cells harboring somatic mutations represent a minimum of 4% of all BM cells (corresponding to a minimum of 2% of the mutation allelic frequency). Subsequently, clonal hematopoiesis gradually increases and ultimately becomes the predominant cell population in the BM, which is called MDS or clonal cytopenia of undetermined significance (CCUS). The abnormal hematopoiesis caused by clonal dominance is frequently linked to additional somatic mutations. Ultimately, the emergence of additional driver mutations acquirement or preexisting mutations results in the selection and leukemic transformation of subclones of hematopoietic cells (highlighted in pale pink) with progressively damaged capacity for differentiation