Polycythemia Vera, Myelofibrosis and Essential Thrombocythemia: Identification of PV, MF & ET Genes

The purpose of this project is to find genes whose mutations cause Polycythemia Vera, Essential Thrombocythemia and Primary Myelofibrosis.

Sex

All

Inclusion Criteria:

1. Patients with an elevated hemoglobin concentration (\>18 in males and \>16 in females) and who are suspected to have congenital or acquired primary polycythemia
2. Patients with a persistent thrombocytosis (\>400,000) that does not have an obvious secondary cause
3. Patients with a bone marrow biopsy that shows increased cellularity and fibrosis
4. Patients where there is clinical concern for primary myelofibrosis, such as anemia in combination with leukocytosis, thrombocytosis, splenomegaly and/or a leukoerythroblastic blood smear
5. Patients with thrombosis at unusual sites, such as Budd-Chiari syndrome, can have early PV before hemoglobin is elevated, these patients will also be included.

Exclusion Criteria:

1. Subjects who have a known acquired cause of polycythemia (increased hemoglobin/hematocrit) such as people living in high altitudes (in excess of 14,000 feet), subjects with heart disease, left to right heart shunt, severe hypoxia or severe pulmonary disease will be excluded from this study.
2. Subjects with a known acquired cause of thrombocytosis.
3. Subjects will be excluded if they cannot demonstrate decision making capacity sufficient to agree or decline the blood drawing or use of their blood for the study.

• BACKGROUNDJelinek J, Li J, Mnjoyan Z, Issa JP, Prchal JT, Afshar-Kharghan V. Epigenetic control of PRV-1 expression on neutrophils. Exp Hematol. 2007 Nov;35(11):1677-83. doi: 10.1016/j.exphem.2007.09.008. PMID 17976520
• BACKGROUNDAgarwal N, Mojica-Henshaw MP, Simmons ED, Hussey D, Ou CN, Prchal JT. Familial polycythemia caused by a novel mutation in the beta globin gene: essential role of P50 in evaluation of familial polycythemia. Int J Med Sci. 2007 Oct 4;4(4):232-6. doi: 10.7150/ijms.4.232. PMID 17952198
• BACKGROUNDGaikwad A, Verstovsek S, Yoon D, Chang KT, Manshouri T, Nussenzveig R, Cortes J, Vainchenker W, Prchal JT. Imatinib effect on growth and signal transduction in polycythemia vera. Exp Hematol. 2007 Jun;35(6):931-8. doi: 10.1016/j.exphem.2007.03.012. PMID 17533047
• BACKGROUNDChen GL, Prchal JT. X-linked clonality testing: interpretation and limitations. Blood. 2007 Sep 1;110(5):1411-9. doi: 10.1182/blood-2006-09-018655. Epub 2007 Apr 13. PMID 17435115
• BACKGROUNDGaikwad A, Nussenzveig R, Liu E, Gottshalk S, Chang K, Prchal JT. In vitro expansion of erythroid progenitors from polycythemia vera patients leads to decrease in JAK2 V617F allele. Exp Hematol. 2007 Apr;35(4):587-95. doi: 10.1016/j.exphem.2006.12.007. PMID 17379069
• BACKGROUNDHoffman R, Prchal JT, Samuelson S, Ciurea SO, Rondelli D. Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment. Biol Blood Marrow Transplant. 2007 Jan;13(1 Suppl 1):64-72. doi: 10.1016/j.bbmt.2006.11.003. PMID 17222772
• BACKGROUNDNussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S, Prchal JF, Prchal JT. Polycythemia vera is not initiated by JAK2V617F mutation. Exp Hematol. 2007 Jan;35(1):32-8. doi: 10.1016/j.exphem.2006.11.012.