One prevailing hypothesis is that KIT D816V is likely to be an early genetic hit in a ‘stem cell’ that gives rise to mast cells (the SM component) and cells of myeloid lineage (the AHNMD component), which likely is followed by a second hit in the AHNMD component, resulting in the development of a more aggressive form of the disease including SM-CMML, SM-MDS and SM-AML [2]. The gene discussed is KIT; the disease is chronic myelomonocytic leukemia.