Ilaria Crespiatico, Mattia Zaghi, Cristina Mastini, Deborah D'Aliberti, Mario Mauri, Carl Mirko Mercado, Diletta Fontana, Silvia Spinelli, Valentina Crippa, Elena Inzoli, Beatrice Manghisi, Ivan Civettini, Daniele Ramazzotti, Valentina Sangiorgio, Michele Gengotti, Virginia Brambilla, Andrea Aroldi, Federica Banfi, Cristiana Barone, Roberto Orsenigo, Ludovica Riera, Mara Riminucci, Alessandro Corsi, Massimo Breccia, Alessandro Morotti, Daniela Cilloni, Aldo Roccaro, Antonio Sacco, Fabio Stagno, Marta Serafini, Federica Mottadelli, Giovanni Cazzaniga, Fabio Pagni, Roberto Chiarle, Emanuele Azzoni, Alessandro Sessa, Carlo Gambacorti-Passerini, Elena Maria Elli, Luca Mologni, Rocco Piazza
SETBP1 mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because 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 marrow fibrosis, prompting us to investigate SETBP1 mutations in a cohort of 36 triple-negative primary myelofibrosis (TN-PMF) cases...
April 4, 2024: Blood