Molecular Pathology of Myeloid Neoplasms

Despite the apparent complexity of the molecular genetic underpinnings of myeloid neoplasms, most myeloid mutational profiles can be understood within a simple framework. Somatic mutations accumulate in hematopoietic stem with aging and toxic insults, termed clonal hematopoiesis. These old stem cells mutations, predominantly in the epigenetic and RNA spliceosome pathways, act as founding driver mutations leading to a clonal myeloid neoplasm when sufficient in number and clone size. Subsequent mutations can create the genetic flavor of the myeloid neoplasm (backseat drivers) due to their enrichment in certain entities or act as progression events (aggressive drivers) during clonal evolution.