How predictive is the finding of clonal hematopoiesis for the development of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML)?

Clonal hematopoiesis (CH) - a biological state in which one or a small number of hematopoietic stem or progenitor cells contribute disproportionately to blood cell production, usually as a result of somatic gene mutations in the stem cells - is often considered to be a precursor to myeloid neoplasia, especially myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, the majority of people with CH never develop an overt myeloid neoplasm, and CH can be a precursor to lymphoid cancers as well as myeloid neoplasms. In addition, CH increases all cause mortality and augments the risk of several non-neoplastic medical conditions, including atherosclerotic cardiovascular disease. CH can arise during aging, or in the context of an inherited marrow failure syndrome, aplastic anemia, or hematopoietic cell transplantation. Risk factors for progression of CH to myeloid neoplasia include larger clone size; the presence of a TP53, IDH1/2, or splicing mutation; multiple mutations; and associated cytopenias or abnormal red blood cell indices. The receipt of genotoxic chemotherapy or radiation, which can promote clonal expansion of mutant clones at the expense of healthy progenitor cells, may result in therapy-related MDS/ AML.

Automated summary

Clonal hematopoiesis (CH) is a biological state where a small number of mutated hematopoietic stem cells disproportionately contribute to blood cell production, potentially leading to myeloid neoplasms. However, not all individuals with CH develop myeloid neoplasms, and CH can also be a precursor to lymphoid cancers. Risk factors for progression to myeloid neoplasms include clone size, specific gene mutations, and exposure to genotoxic therapies.