At Aptel Research, we stay on top of new advancements in biotechnology and the pharmaceutical industry. These days there is more and more attention onmyeloproliferative disorders, mostly due to the discovery in 2005 of a mutation that is present in a substantial proportion of myelofibrosis (MF), polycythemia vera (PV), and essential thrombocytosis (ET) patients. These diseases are hematological malignancies that cause red blood cells, white blood cells and platelets to grow abnormally in bone marrow. The discovery of a common mutation in the JAK2 protein, has lead to an increase in the number of possible therapies to treat the disorders, and the hope that we still may find a cure.
Janus kinase 2 (JAK2) is a protein tyrosine kinase that is involved in cell proliferation and cell survival. A mutation here causes sustained signaling, and leads to hematological malignancies. JAK1 and JAK3 are two other proteins in this family of kinases. JAK1 is similar to JAK2, and it is believed that inhibition of this signal, could have an effect on cancers. JAK3 is involved predominantly in immune cells, and its inhibition would lead to immunosuppression. While the JAK2 inhibitors are still in clinical trials, it is hoped that these therapies will lead to more effective treatment of a group of diseases that have had few other developments in recent years.
Myelofibrosis can transform from polycythemia vera, or from essential thrombocytosis, or can arise independently of these other myloproliferative disorders. This disease results in production of too few red blood cells, fibrosis (or scaring) of the bone marrow, and eventually bone marrow failure. The disease is rare, and extremely heterogenous, with clinical symptoms ranging from fatigue to an extremely enlarged spleen. The life expectancy for an MF patient can range from 3 to 10 years following diagnosis. Currently, the treatment goal is improving quality of life, as there is no therapy that is able to alter the natural history of the disease. In select cases, allogenic stem cell transplantation may be preformed. This is the only way to cure myelofibrosis.
While myelofibrosis is characterized by low production of red blood cells, polycythemia vera is marked by high production of red blood cells. The higher viscosity of the blood increases risk for thrombosis (blood clots), which is of great clinical concern. The life expectancy of PV patients is much greater than that of MF patients; it averages 20 years from diagnosis. Treatment of PV includes phlebotomy and aspirin.
The third myeloproliferative disorder is essential thrombocytosis (ET), which is characterized by elevated platelet count. Both PV and ET patients can be without clinical symptoms, but occasionally present with headaches or visual disturbances. ET patients are also at an increased risk for thrombosis, who otherwise have a normal life expectancy. These patients can usually be treated with aspirin.
So far, clinical data from the JAK2 inhibitor trials looks extremely promising. This will be the biggest advance in these diseases in decades, and we all await these potential game-changers, and look forward to hearing updates on their progress at ASCO 2011.