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http://mpdfoundation.org/webarticle.htm
A safe treatment for PV may be coming very soon!!!
It's big news! This is truly a major discovery that gives all MPD patients
a great deal to be thankful for. The optimum result will be a drug that
targets the JAK2 mutation, just as Gleevec targets the tyrosine kinase
responsible for CML. That would mean better control of our counts, fewer
side effects and healthier, longer lives . . .
The first news came out on March 17, 2005: A team of researchers at
the Cambridge Institute for Medical Research, UK, led by Dr. Tony Green,
announced that they had discovered a single point mutation in the JAK2
gene that appeared in 97% of polycythemia vera patients they studied
. . .
Discoveries Reveal Gene Mutation That Causes Blood Disorders
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.
SOURCE American Society of Hematology --------------------------------------------------------------------------------
Related links: http://www.hematology.org --------------------------------------------------------------------------------
Issuers of news releases and not PR Newswire are solely responsible
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on redistribution, apply. Copyright © 1996-2006 PR Newswire Association
LLC. All Rights Reserved. A United Business Media company.
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Spivak2003
article: Here is a very technical but up-to-date and comprehensive
article summarizing much of the most current PV research . . . A
must read for your doctor. Below are some important highlights of
the article.
Phlebotomy to reduce the red cell mass and keep it at a safe
level (hematocrit < 45%) remains the cornerstone of treatment.
Venesection is an effective and safe therapy and previous concerns about
potential side effects, including severe iron deficiency and an increased
tendency to thrombosis or myelofibrosis, were erroneous. Many patients
require no other therapy for many years. For others, however, poor compliance
to phlebotomy or progressive myeloproliferation, as indicated by increasing
splenomegaly or very high leukocyte or platelet counts, may call for
the introduction of cytoreductive drugs. In ET, the therapeutic trade-off
between reducing thrombotic events and increasing the risk of leukemia
with the use of cytoreductive drugs should be approached by patient
risk stratification. Thrombotic deaths seem very rare in low-risk ET
subjects and there are no data indicating that fatalities can be prevented
by starting cytoreductive drugs early. Therefore, withholding chemotherapy
might be justifiable in young, asymptomatic ET patients with a platelet
count below 1,500,000/mm3 and with no additional risk factors for thrombosis.
Aspirin treatment lowered the risk of cardiovascular death, non-fatal
myocardial infarction, and non-fatal stroke (relative risk 0.41 [95%
CI 0.15–1.15], P = .0912). Total and cardiovascular mortality were also
reduced by 46% and 59%, respectively. Major bleedings were slightly
increased nonsignificantly by aspirin.
Oct 30,2005
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