Myeloproliferative Diseases

The myeloproliferative diseases (MPDs) are a group of diseases of the bone marrow in which excess blood cells are produced; these include polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). The prevalence of MPDs in the United States has been estimated at 80,000–100,000 cases, with ~2–5 new cases per 100,000 per year. While current therapies consist of hydroxyurea or interferon-alpha treatment and/or phlebotomy, there is still a dire need for additional therapies to treat patients diagnosed with these disorders.

In patients afflicted with PV, erythropoiesis, the production of red blood cells that takes place in the bone marrow throughout life, is disrupted resulting in an overabundance of these cells.  This excess can lead to the formation of blood clots and cause life-threatening illness. miRagen collaborators recently showed that microRNA-451 (miR-451) regulates erythropoiesis in vivo (Patrick et al., Genes & Dev., 2010). Importantly, mice lacking miR-451 display a reduction in hematocrit, the measurement of red blood cells in ratio to blood volume. They also display a defect in the process by which red blood cells or their precursors are differentiated in response to oxidative stress. These findings reveal an essential role for miR-451 in proerythroid differentiation and highlight the therapeutic potential of miR-451 inhibitors in the treatment of polycythemia vera, red cell dyscrasias generally, or other hematopoietic malignancies.