Il-1r1 drives leukemogenesis induced by Tet2 loss

Abstract

Loss of the ten-eleven translocation methylcytosine dioxygenase 2 ( Tet2 ) gene, which is commonly mutated in hematological malignancies, dysregulates inflammatory pathways, including the interleukin-1 (IL-1) pathway [ 1 , 2 , 3 ]. Roles for IL-1 signaling have been reported in terminally differentiated hematopoietic cells and in non-cell autonomous contexts [ 3 , 4 ]. However, our group demonstrated that inhibition of inflammatory pathways can suppress clonal hematopoiesis (CH), indicating potential direct roles for hematopoietic stem and progenitor cells (HSPCs) in inflammation [ 5 ]. As TET2 mutations are often present in HSPCs and provide these cells with a competitive advantage, dysregulation of the IL-1 pathway in HSPCs may contribute to leukemogenesis and may catalyze the progression of preleukemic states to malignancy [ 6 ].