Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host

Posted by: | May 21, 2018 | Comments

ABSTRACT

Tet2 deficiency leads to systemic bacterial dissemination

Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies1,2,3,4,5,6,7. In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage1,4,8,9. However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2−/− mice8,9 and humans with TET2 mutations1,3,5,6,7, suggesting that extrinsic non-cell-autonomous factors are required for disease onset. Here we show that bacterial translocation and increased interleukin-6 production, resulting from dysfunction of the small-intestinal barrier, are critical for the development of PMP in mice that lack Tet2 expression in haematopoietic cells.

Read more at: Nature

Marlies Meisel, et al. Nature. DOI: doi:10.1038/s41586-018-0125-z. 16 May 2018.





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