Fig. 3

Concurrent genetic mutations of TET2^MT human myeloid malignancies. A. Mutations of ASXL1, SRSF2, DNMT3A, and EZH2 concur in all types of myeloid malignancies. Second allele mutations of TET2 are commonly detected in MDS and MPNs but not in de novo AML. In addition, mutations in splicing factors such as SF3B1 and U2AF1 are commonly detected in MDS, while mutations of signaling molecules are commonly detected in MPN and AML patients. B Idh1/2 regulate the production of α-KG and promote TET2 activity, whereas mutant Idh1/2 regulate the production of 2HG and repress TET2 activity. TET2 regulates the differentiation of myeloid progenitors primarily by interacting with WT1 for DNA binding. Mutations of Idh1/2 and WT1 are exclusive in TET2^MT myeloid malignancies. (Created with BioRender.com)