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. Author manuscript; available in PMC: 2017 Jun 30.
Published in final edited form as: Exp Hematol. 2015 Oct 9;43(12):989–992. doi: 10.1016/j.exphem.2015.08.012

Figure 1. Schematic representation of mutational cooperativity during leukemogenesis.

Figure 1

Individual mutations in genes that impact on DNA methylation such as TET2 or IDH1/2, remodel the DNA methylome of normal HSCs resulting in enhanced self-renewal, but do not provide the necessary proliferation stimulus to drive leukemic transformation. In contrast, mutations in the tyrosine kinase receptor FLT3 drive proliferation, leading to the onset of a myeloproliferative neoplasm but lacking the ability to directly precipitate acute leukemia. Combined mutation of TET2/IDH and FLT3 facilitates a synergistic reprogramming of key genetic loci which is required for leukemic transformation and is likely required the maintenance of leukemia propagating cells.