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.

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].

This article originally appeared on Cancer Therapy Advisor