Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders

June 30, 2017 updated by: National Institutes of Health Clinical Center (CC)
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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment (Actual)

8

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • District of Columbia
      • Washington, D.C., District of Columbia, United States, 20422
        • VA Medical Center, Washington D.C.
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institutes of Health Clinical Center (CC)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 6, 2007

Study Completion

May 19, 2010

Study Registration Dates

First Submitted

February 9, 2007

First Submitted That Met QC Criteria

February 9, 2007

First Posted (Estimate)

February 12, 2007

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

May 19, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 070090
  • 07-CC-0090

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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