TET2 Loss May Indirectly Cause Hematologic Oncogenesis

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TET2 loss may indirectly cause several hematologic malignancies, including myeloid, T cell, and B cell cancers.
TET2 loss may indirectly cause several hematologic malignancies, including myeloid, T cell, and B cell cancers.

TET2 loss may indirectly cause several hematologic malignancies, including myeloid, T cell, and B cell cancers, according to a study published in Nature Communications.1

TET2 is frequently mutated or deleted in myeloid malignancies, including acute myeloid leukemias, B cell non-Hodgkin lymphomas, chronic myelomonocytic leukemias, and myelodysplastic syndromes. TET2 mutations are also found in more than 5% of healthy people older than 70 years. 

While TET2 loss is linked to hematopoietic stem cell (HSC) self-renewal and hematopoietic progenitor cell (HPC) activity, each of which plays a role in oncogenesis and tumor suppression, respectively, the exact factors linking TET2 loss/mutation to hematologic oncogenesis are unknown.

For this mouse model study, researchers used data from 265 mice to determine the hematologic malignancies associated with TET2 loss.

TET2-/- mice (198 of 265) all developed a lethal hematologic malignancy within 2 years, while “no abnormalities” were noted in the hematopoietic organs of the 67 TET2-wildtype mice.

TET2-/- mice developed any of myeloid, T cell, or B cell malignancies.

The authors also found that while TET2 loss led to “hypermutagenicity in HSCs/HPCs,” these mutated cells were not necessarily themselves malignant, though they likely lead to other driver mutations.

RELATED: Abnormal Uterine Bleeding May Signal Hematologic Cancer

The authors concluded that these results “provide additional insights into the mechanisms by which loss-of-function TET2 mutations cause diverse human haematological malignancies.”

Reference

  1. Pan F, Wingo TS, Zhao Z, et al. Tet2 loss leads to hypermutagenicity in haematopoietic stem/progenitor cells. Nat Commun. 2017 Apr 25. doi: 10.1038/ncomms15102 [Epub ahead of print].

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