HSC compartment and modes of clonality of hematopoiesis in bone marrow failure (A) Clonality or oligoclonality can be due to HSC depletion (eg, in some cases of AA) or a true subclonal expansion. (B) Transient clonal evolution in AA. (C) Theories about secondary MDS evolution in the context of AA. Mutant (clonal) HSC can already exist at presentation with subsequent selection (top), or the clonogenic hits occur in the course of disease (eg, as a result of endogenous/immune-mediated mutagenesis [bottom]). (D) Progressive linear acquisition of mutations as seen in typical MDS. CTL, cytotoxic T lymphocyte; GF, growth factor.