Presentation description

Myelofibrosis (MF) is a hematopoietic stem cell disorder characterized by bone marrow fibrosis that disrupts normal blood cell production. This leads to severe anemia, weakness, fatigue, and an enlarged spleen. Inflammatory cytokine levels are elevated in MF patients' bone marrow and peripheral blood. In particular, tumor necrosis alpha (TNF) levels are increased and are associated with disease progression. YTHDF2 is an mRNA reader that has been shown to decrease the half-life of diverse m6A transcripts, including the tumor necrosis factor receptor 2 (TNFR2). TNF signaling is mediated through the combined actions of TNF receptor 1 (TNFR1) and receptor 2 (TNFR2), whose contributions can alter the balance between pro-survival and apoptotic signaling. Here, we show that knockout of YTHDF2 in hematopoietic stem and progenitor cells increases/decreases cell growth in the presence of TNF.