Figure 6.

The proposed model of multistage development in AITL. Mutations in DNA methylation regulators—namely TET2, DNMT3A, and IDH2—are early events, with TET2 and DNMT3A mutation occurring in hematopoietic stem cells. These mutations enhance the self‐renewal of haematopoietic stem cells, increase the risk of lymphomagenesis, and may frequently generate bi‐ or oligoclonal T‐cell populations in AITL or PTCL‐TFH following acquisition of additional genetic changes in genes important for T‐cell biology. The TET2 mutant hematopoietic progenitor cells also give rise to non‐neoplastic polyclonal B and CD8 positive T‐cells as reported in several previous studies 7, 13, 14, 16, 21. Finally, there is also a possibility that minor T‐cell clones are not related to TET2 or DNMT3A mutation but are the consequence of immunodeficiency and EBV reactivation in patients with AITL.