Clonality in context: hematopoietic clones in their marrow environment

Clonal hematopoiesis occurs normally, especially with aging, and in the setting of disease, not only in myeloid cancers but in bone marrow failure as well. In cancer, malignant clones are characterized by recurrent somatic mutations in specific sets of genes, but the direct relationship of such mutations to leukemogenesis, when they occur in cells of an apparently healthy older individual or after recovery from immune aplastic anemia, is uncertain. Here we emphasize a view of clonal evolution that stresses natural selection over deterministic ontogeny, and we stress the selective role of the environment of the marrow and organism. Clonal hematopoieses after chemotherapy, in marrow failure, and with aging serve as models. We caution against the overinterpretation of clinical results of genomic testing in the absence of a better understanding of clonal selection and evolution.