ATLANTA, Dec. 11 /PRNewswire/ -- Several members of the American Society of Hematology (ASH) have discovered a single point mutation in the JAK2 gene that is expressed in a high percentage of patients with one of three myeloproliferative diseases. The discovery of this mutation may lead to the development of a targeted therapy to combat these disorders.
Myeloproliferative diseases (MPDs) are a closely related group of blood disorders characterized by excessive production or dysfunction of blood cells. The three main MPDs are polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis. The actual incidence of MPDs is difficult to measure, but the most complete statistics to date estimate that they affect 4.7 people out of every 100,000. There is currently no known cure for MPDs.
Polycythemia vera is characterized by an increase in the number of red blood cells, often accompanied by an elevated white blood cell count, an elevated platelet count, an enlarged spleen, and a propensity to develop pathological thrombosis. Essential thrombocythemia is characterized by a proliferation of megakaryocytes in the bone marrow, leading to an increased number of circulating platelets and a similar tendency to develop abnormal blood clotting. Idiopathic myelofibrosis is a disorder in which too few red blood cells, white blood cells, and platelets are made resulting from abnormal growth of fibrous tissue within the marrow due to abnormalities of the blood- forming cells.
Kenneth Kaushansky, M.D., professor and chair of the Department of Medicine at the University of California, San Diego, will lead a special plenary session on the origins and effects of these JAK2 disorders at the 47th Annual Meeting of ASH. The ASH annual meeting is the world’s largest gathering of hematologists, the specialists who treat blood diseases and disorders.
“There has been an explosion of new knowledge beginning with the discovery earlier this year of the role of the JAK2 V617F mutation in polycythemia vera, myelofibrosis, and essential thrombocythemia, providing novel insight into the molecular basis of pathological myeloproliferation,” said Dr. Kaushansky. “Because this discovery reveals key information about the pathophysiology of MPDs, it was decided that the issue should be discussed before all attendees of the ASH annual meeting.”
JAK2 is a protein tyrosine kinase, an enzyme that adds a phosphate group to numerous cellular proteins involved in transmitting growth signals that trigger the production of blood cells. The V617F mutation causes the constitutive activation of these molecular signaling pathways, leading to the uncontrolled cell proliferation for which the myeloproliferative disorders are named. Abnormal regulation or function of tyrosine kinases have been implicated in many cancers, including chronic myelogenous leukemia (CML), the treatment of which was revolutionized with the discovery of imatinib mesylate (commonly known as Gleevec). Imatinib mesylate targets the tyrosine kinase responsible for the abnormal proliferation of white blood cells that characterizes this disease.
Several abstracts scheduled for presentation during the ASH annual meeting examine the JAK2 discovery. A research team led by Anthony Green, M.D., of Cambridge University (Abstract 253) noted that the JAK2 mutation occurs in most patients with polycythemia vera, but only half of those with essential thrombocythemia and idiopathic myelofibrosis. Dr. Green’s analysis revealed JAK2 mutation status divided essential thrombocythemia into two biologically distinct subtypes with those patients carrying the V617F mutation having disease characteristics that closely resembled polycythemia vera.
“Our results suggest that V617F-positive essential thrombocythemia and polycythemia vera are closely related and have major implications for the classification, diagnosis, and management of MPDs,” according to Dr. Green. Abstract 253 will be presented on Monday, December 12, 2005, at 7:30 a.m. ET.
Researchers from the Mayo Clinic and Dana-Farber Cancer Institute (Abstract 254) also examined the relationship between essential thrombocythemia and polycythemia vera relating to the JAK2 mutation. Essential thrombocythemia patients with the V617F mutation had disease characteristics commonly associated with polycythemia vera, but they were unsure whether that was relevant when selecting the best treatment option. Abstract 254 will be presented on Monday, December 12, 2005, at 7:45 a.m. ET.
“More research needs to be completed, but we may be on the brink of developing targeted therapies to treat MPDs,” says Dr. Kaushansky. “The identification of a potential molecular target is a major discovery that may one day benefit patients, but not all MPD patients have the JAK2 mutation. Researchers are continuing to look for other mutations that may be associated with MPDs. It is hoped that open discussion of new findings and remaining questions will spur additional insights into the origins and control of these disorders.”
Dr. Kaushansky will moderate a plenary session titled “Myeloproliferative Diseases Revealed: The Molecular Basis and Potential for Targeted Therapy of Polycythemia Vera, Idiopathic Myelofibrosis, and Essential Thrombocythemia” on Sunday, December 11, from 1:45 - 2:45 p.m. ET. To arrange an interview with Dr. Kaushansky, please call the ASH Media Room at 404-222-5705.
The American Society of Hematology (http://www.hematology.org) is the world’s largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems, by promoting research, clinical care, education, training, and advocacy in hematology.
American Society of Hematology
CONTACT: Aislinn Raedy of the American Society of Hematology,+1-202-776-0544, araedy@hematology.org, On-Site (12/9 - 12/13):+1-404-222-5705
Web site: http://www.hematology.org//