JAK2 and leukemia: Driver mutations conferring HSCs with selective advantages (i.e., in DNMT3A, JAK2, ASXL1, TET2 and others) lead to clonal expansion in aged individuals, who do not (yet) suffer from leukemia or MDS.117 During further tumor progression, cancer cells frequently respond to their altered state by undergoing programmed cell death and remain highly dependent on certain survival signals from their environment.118, 119 Within a growing tumor, apoptosis will preferentially eliminate those sub-clones with the highest apoptosis sensitivity whereas sparing the more resistant cells.