Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00433862
First received: February 9, 2007
Last updated: May 20, 2010
Last verified: May 2010
  Purpose

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases characterized by proliferation of one or more hematopoietic lineages. Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. This mutation confers constitutive activity on to the JAK2 protein and appears to play an important role in the pathobiology of these conditions. However, not all patients with myeloproliferative disorders have this mutation and it may not be the primary cause of these diseases. The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. Approximately, 150 patients with myeloproliferative disorders will be studied over 3 years. The studies will involve the collection of 40 mL to 50 mL of peripheral blood from each subject. The blood will be used to assess neutrophil gene and protein expression, gene polymorphisms, and plasma protein levels.


Condition
Polycythemia Vera
Essential Thrombocytosis
Idiopathic Myelofibrosis
Neutrophils
Chronic Myeloproliferative Disorders

Study Type: Observational
Study Design: Time Perspective: Prospective
Official Title: Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 8
Study Start Date: February 2007
Estimated Study Completion Date: May 2010
Detailed Description:

The three main chronic myeloproliferative disorders are polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). These are clonal neoplastic diseases characterized by proliferation of one or more hematopoietic lineages. Recently a mutation of the Janus Kinase 2 (JAK2) gene that leads to the substitution of phenylalanine for valine at position 617 of the JAK2 protein, JAK2 V617F, has been found in 76% to 97% of patients with PV, 29% to 57% of patients with ET and 50% of patients with IMF. This mutation confers constitutive activity on to the JAK2 protein and appears to play an important role in the pathobiology of these conditions. However, not all patients with myeloproliferative disorders have this mutation and it may not be the primary cause of these diseases. The primary goal of this prospective natural history study is to investigate the molecular basis of these diseases in groups of patients who have JAK2 V617F and in those who do not. A second goal is to identify biomarkers for PV and the other myeloproliferative disorders that are easier to measure than JAK2 V617F. Approximately, 150 patients with myeloproliferative disorders will be studied over 3 years. The studies will involve the collection of 40 mL to 50 mL of peripheral blood from each subject. The blood will be used to assess neutrophil gene and protein expression, gene polymorphisms, and plasma protein levels.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Diagnosis or suspected diagnosis of PV, ET, or IMF. The World Health Organization Criteria will be used for diagnosing this disorder. In brief, the criteria for PV is hemoglobin greater than 18.5 g/dL in men and greater than 16.5 g/dL in women and splenomegaly on palpation in the absence of secondary erythrocytosis. If splenomegaly is absent, the patient must have 2 of the following 4 minor criteria: platelet count greater than 400 x 10(9)/L, leukocyte count greater than 12 x 10(9)/L, marrow biopsy with trilineage increase in cellularity, and low serum erythropoietin level. The criteria for EF is a platelet count greater than 600 x 10(9)/L with no known cause of reactive thrombocytosis and a normal hemoglobin. The criteria for IMF is fibrosis of the bone marrow and splenomegaly without preceding PV, ET or chronic myelogenous leukemia.
    2. Both male and female subjects will be studied.
    3. Any ethnic group.
    4. 18 years of age or older.

EXCLUSION CRITERIA:

Subjects will be excluded if they have any of the following conditions:

  1. Increased blood counts due to a disease other than chronic myeloproliferation.
  2. Know history of anemia (hematocrit less than 12.0 mg/dL).
  3. Pregnancy.
  4. Infection with HIV, hepatitis B, or hepatitis C.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433862

Locations
United States, District of Columbia
VA Medical Center, Washington D.C.
Washington, District of Columbia, United States, 20422
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00433862     History of Changes
Other Study ID Numbers: 070090, 07-CC-0090
Study First Received: February 9, 2007
Last Updated: May 20, 2010
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Polycythemia Vera
Essential Thrombocytosis
Idiopathic Myelofibrosis
Janus Kinase 2
CD177
Chronic Myeloproliferative Disorders
PV
Essential Thrombocythemia
ET
IM

Additional relevant MeSH terms:
Primary Myelofibrosis
Myeloproliferative Disorders
Polycythemia
Polycythemia Vera
Thrombocythemia, Essential
Thrombocytosis
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on August 28, 2014