Gene expression profile of HSPC with cell-intrinsic innate immune signaling activation after LPS treatment

The underlying mechanisms responsible for the competitive advantage of MDS HSPC in an inflammatory milieu remains poorly defined. Here, we show that MDS HPSC are protected from low-grade chronic inflammation, and that the adaptive response of these cells to the inflammatory milieu via the non-canonical NF-κB pathway contributes to sustained myeloid expansion and a competitive advantage. These findings uncover the mechanistic basis for the clonal dominance of functionally impaired MDS HSPC and reveal the therapeutic potential of interfering with non-canonical NF-κB signaling. mRNA profiles of human miR-146a deficient and WT CD34+ BM cells, Vav-TRAF6 and WT LSK murine BM cells, or Tet2F/F and Tet2F/F;VavCre murine BM cells treated with either PBS or LPS for 90 min.