apatorsen and Primary-Myelofibrosis

Heat shock protein 27 (HSP27/HSPB1) is a stress-inducible chaperone that facilitates cancer development by its proliferative and anti-apoptotic functions. The OGX-427 antisense oligonucleotide against HSP27 has been reported to be beneficial against idiopathic pulmonary fibrosis. Here we show that OGX-427 is effective in two murine models of thrombopoietin- and JAKV617F-induced myelofibrosis. OGX-427 limits disease progression and is associated with a reduction in spleen weight, in megakaryocyte expansion and, for the JAKV617F model, in fibrosis. HSP27 regulates the proliferation of JAK2V617F-positive cells and interacts directly with JAK2/STAT5. We also show that its expression is increased in both CD34

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cell Line, Tumor; Disease Models, Animal; Female; HEK293 Cells; HSP27 Heat-Shock Proteins; Humans; Janus Kinase 2; K562 Cells; Leukocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Targeted Therapy; Mutation; Oligonucleotides; Primary Myelofibrosis; STAT5 Transcription Factor; Thrombopoietin; Transduction, Genetic; Whole-Body Irradiation