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

ABSTRACT: 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

SUBMITTER: Meisel M 

PROVIDER: S-EPMC6238954 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature