Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders
Molecular Changes and Biomarkers in Chronic Myeloproliferative Disorders
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.
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.
-  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.