Figure 4

Schematic representation of pathways leading to acute myeloid leukemia (AML) from hematopoietic stem cell (HSC) or progenitors (PG). Gene fusions and NPM1 mutation are major events in the induction of primary AMLs with favorable and intermediate cytogenetic risk (they correspond respectively to mutation groups A and B of Ley et al [24], and to mutation groups 2 + 3 and 1 of Shen et al. [101]. Secondary AML following MPN or MDS (see Figure 1) could occur after a series of gene mutations in transcription factors and epigenetic regulators combined with a mutation in a signaling pathway (see Figure 3), after TP53 mutation and a series of mutations and karyotype alterations due to genetic instability, or after additional mutations in BCR-ABL chronic myeloid leukemia.