Figure 1.

Mechanisms of sAML ontogenesis. Myeloid mutations are spontaneously acquired in the bone marrow with ageing, due to natural genotoxicities; specific genotoxic events may exacerbate the rate of mutations. Leukemic transformation happens toward different putative mechanisms. (A) sAML alterations may be acquired via a one-step catastrophic event in an elsewhere normal stem cell. (B) A cell containing a single leukemia-predisposing alteration may evolve via a leukemia-promoting “second hit”. (C) Time-dependent accumulation of several myeloid alterations may cause sAML via acquisition of a leukemia-promoting event. (D) A leukemia-promoting event may be acquired in a subclone in an oligoclonal bone-marrow with plenty of myeloid genes mutations.