Scientists have announced new discoveries about the role of TET2 gene deficiency in the development of acute myeloid leukaemia (AML).
Up to 20% of AML cases have deficiency of or mutations in the TET2 gene. This speeds up the development of leukaemia, driven by other mutations and translocations. However, the exact mechanisms of how TET2 increases leukaemogenesis have not been fully understood.
So a research team, led by Dr Jianjun Chen of the City of Hope National Medical Center in Duarte, California, USA, set out to explore the process in more depth.
The team carried out tests on laboratory models and mouse models of AML. They found that TET2 deficiency increases the movement of leukaemia stem cells into a particular bone marrow niche, and increases their self-renewal.
In addition, a lack of the TET2 gene in acute myeloid leukaemia blast cells increases levels of a cell surface protein called Tetraspanin 13. This leads to even greater movement of leukaemia stem cells into the bone marrow niche.
“Collectively, our studies reveal the functional importance of TET2 in leukemogenesis, leukemic blast cell migration/homing, and leukaemia stem cell self-renewal,” they conclude.
Dr Chen said: “This study provides novel insights into the cellular and molecular mechanisms underlying the development of acute myeloid leukaemia. Our findings highlight the therapeutic potential of reactivating TET2 signalling in patients with TET2 mutations or transcriptional suppression.
“Equally exciting, this strategy could be applied to other types of cancer that feature TET2 deficiency.”
Li Y, Xue M, Deng X, Dong L, Nguyen LXT, Ren L, Han L, Li C, Xue J, Zhao Z, Li W, Qing Y, Shen C, Tan B, Chen Z, Leung K, Wang K, Swaminathan S, Li L, Wunderlich M, Mulloy JC, Li X, Chen H, Zhang B, Horne D, Rosen ST, Marcucci G, Xu M, Li Z, Wei M, Tian J, Shen B, Su R, Chen J. (2023) “TET2-mediated mRNA demethylation regulates leukemia stem cell homing and self-renewal.” Cell Stem Cell, doi: 10.1016/j.stem.2023.07.001
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