Figure 1.

Dynamic stochastic model of impaired differentiation in granulocyte precursors. GCSF signaling occurs through its cognate receptor, GCSFR. It involves both proximal signaling networks consisting of signaling molecules such as Lyn, Jak, STAT, Akt, and ERK, and distal gene regulatory networks consisting of transcription factors. Together, these signaling networks promote proliferation, survival, and differentiation. In patients with severe congenital neutropenia, the earliest known mutation to contribute to transformation to secondary MDS or AML is a nonsense mutation in the GCSFR gene. This mutation leads to a truncated receptor, GCSFR delta 715.