Preclinical studies on the use of a P-selectin-blocking monoclonal antibody to halt progression of myelofibrosis in the Gata1low mouse model

Myelofibrosis (MF) is the most severe of Philadelphia chromosome –negative myeloproliferative neoplasms (MPN). The complex phenotype of patients with MF includes fibrosis and hematopoietic failure in bone marrow (BM), stem/progenitor cell mobilization, and development of extramedullary hematopoiesis with splenomegaly, and their clinical course is associated wit h an increased risk of thrombosis, bleeding, and evolution to acute leukemia [1–4]. MF may be driven by gain of function mutations in several genes of the thrombopoietin axes, such as MPL, the thrombopoietin receptor; JAK2, the first element of the MPL signaling; and calreticulin, a chaperon prote in, which when mutated binds MPL on the cell surface, inducing conformational changes, leading to ligand-independent constitutive activation of the receptor [5].

Source: Experimental Hematology - September 30, 2022 Category: Hematology Authors: Paola Verachi, Francesca Gobbo, Fabrizio Martelli, Mario Falchi, Antonio di Virgilio, Giuseppe Sarli, Celine Wilke, Andreas Bruederle, Anirudh Prahallad, Francesca Arciprete, Maria Zingariello, Anna Rita Migliaccio Tags: Article Source Type: research