Clonality in context: hematopoietic clones in their marrow environment

James N. Cooper and Neal S. Young


Clonal hematopoiesis occurs normally, especially with aging, and in the setting of disease, not only myeloid cancers but in bone marrow failure. 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 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 marrow's, and organism's, environment. Clonal hematopoiesis after chemotherapy, in marrow failure, and with aging serve as models. We caution against the over interpretation of clinical results of genomic testing in the absence of a better understanding of clonal selection and evolution.

  • Submitted July 7, 2017.
  • Accepted October 4, 2017.