First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis

SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, as SETBP1 mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed a myeloid neoplasm with megakaryocytic dysplasia, splenomegaly, and bone …