From clonal hematopoiesis to myeloid leukemia and what happens in between: Will improved understanding lead to new therapeutic and preventive opportunities?

Clonal hematopoiesis (CH) as defined by the presence of somatic mutations in genes associated with myeloid neoplasms (MN) is common in healthy elderly individuals and does not necessarily constitute a premalignant state. Several acronyms (idiopathic cytopenia of undetermined significance [ICUS], clonal cytopenia of undetermined significance [CCUS], CH of indeterminate potential [CHIP]) related to CH have been coined to describe patients who do not meet the diagnostic criteria for other hematologic disorders. CHIP carries an annual progression rate to MN of 0.5-1.0% as well as an increased risk of cardiovascular mortality and development of therapy-related MN in patients with solid tumors. Further studies on the natural history of ICUS, CCUS, and CHIP and to assess the risk for progression to MN are needed. Herein, we review the current understanding and clinical significance of these conditions to guide physicians in the interpretation of genetic testing results in various clinical settings.