Metformin, a widely used antidiabetic drug, has previously been demonstrated to exert anti-cancer effects in certain hematological malignancies, but its effects on the transformation of myelodysplastic syndromes to acute myeloid leukemia (AML-MDS) remain unclear.
In addition, TET2 is the second-most frequently mutated gene in clonal hematopoiesis in individuals with no apparent blood cancers, suggesting that while TET2 mutations alone are insufficient to cause hematologic malignancy, they represent an early event during tumorigenesis.
Thus, Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells, suggesting a novel TET2 loss-mediated mechanism of haematological malignancy pathogenesis.
Our findings reveal a non-cell-intrinsic, tumor-promoting function for Tet2 and suggest that Tet2 may present a therapeutic target for the treatment of non-hematologic malignancies.
The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin.
Here, we review recent literature on TET2 interactors and discuss their possible roles in TET2 loss-mediated dysregulation of hematopoiesis and pathogenesis of hematological malignancies.
Using TET2 variants encountered in hematologic neoplasms, several examples of this multifactorial approach to classifying sequence variants of unknown significance are presented.
This review summarizes the recently identified TET2 physiological and pathological functions and discusses how this knowledge influences our therapeutic approaches in hematological malignancies and possibly other tumor types.
Here, we summarize the recent results implicating TET2 in hematological malignancies suggesting that further studies are required to fully understand the role of DNA methylation alterations during transformation.
Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.