Meisel et al. 2018 Nature 557: 580–584

Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies (1–7). In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage (1,4,8,9). However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2 −/−mice (8,9) and humans with TET2 mutations (1,3,5–7), 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. Furthermore, in s…