Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 387-397 , September 2006

Polycythemia vera and its molecular basis: An update

  • Josef T. Prchal

      Affiliations

    • Corresponding Author InformationCorresponding author. Address: Division of Hematology/BMT, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, VT 84132, USA. Tel.: +1 801 581 4220; Fax: +1 801 585 3432.

References 

  1. Beutler E. Polycythemia. In:  Beutler E,  Lichtman MA,  Coller BS, et al. editor. Williams Hematology. 6th edn. New York: McGraw-Hill; 2001;p. 689–701
  2. James C, Ugo V, Le Couedic J-P, et al. A unique clonal JAK2 mutation leading to constitutive signaling causes polycythaemia vera. Nature. 2005;434:1144–1148
  3. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352:1779–1790
  4. Levine R, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7:387–397
  5. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365:1054–1061
  6. Zhao R, Xing S, Li Z, et al. Identification of an Acquired JAK2 Mutation in Polycythemia vera. J Biol Chem 2005; 280: 22788–22792.
  7. Carrel L, Willard HF. X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005;434(7031):400–404
  8. Beutler E, Yeh M, Fairbanks VF. The normal human female as a mosaic of X-chromosome activity: studies using the gene for G-6-PD deficiency as a marker. Proc Natl Acad Sci U S A. 1962;48:9–16
  9. Vogelstein B, Fearon ER, Hamilton SR, Feinberg AP. Use of restriction fragment length polymorphisms to determine the clonal origin of human tumors. Science. 1985;227:642
  10. Fearon ER, Winkelstein JA, Civin CI, et al. Carrier detection in X-linked agammaglobulinemia by analysis of X-chromosome inactivation. N Engl J Med. 1987;316:427–431
  11. Abrahamson G, Fraser NJ, Boyd Y, Craig I. X-chromosome inactivation patterns using HGPRT and PGK polymorphisms in haematologically normal and post chemotherapy females. Br J Haematol. 1990;74:371–372
  12. Gilliland DG, Blanchard KL, Levy J, et al. Clonality in myeloproliferative disorders: analysis by means of the polymerase chain reaction. Proc Natl Acad Sci USA. 1991;88:6848–6852
  13. Curnutte JT, Hopkins PJ, Kuhl W, Beutler E. Studying X-inactivation. Lancet. 1992;339:749
  14. Prchal JT, Guan YL, Prchal JF, Barany F. Transcriptional analysis of the active X-chromosome in normal and clonal hematopoiesis. Blood. 1993;81:269–271
  15. Liu E, Jelinek J, Pastore YD, et al. Discrimination of polycythemias and thrombocytosis by novel, simple, accurate clonality assays and BFU-E response to erythropoietin. Blood. 2003;101:3294–3301
  16. Prchal JT. Polycythemia vera and other primary polycythemias. Curr Opin Hematol. 2005;12:112–116
  17. Kralovics R, Guan Y, Prchal JT. Acquired uniparental disomy of chromosome 9p is a frequent stem cell defect in polycythemia vera. Exp Hematology. 2002;30:229–236
  18. Prchal JF, Axelrad AA. Letter: bone-marrow responses in polycythemia vera. N Engl J Med. 1974;290:1382
  19. Fisher MJ, Prchal JF, Prchal JT, D'Andrea AD. Anti-erythropoietin (EPO) receptor monoclonal antibodies distinguish EPO-dependent and EPO-independent erythroid progenitors in polycythemia vera. Blood. 1994;84:1982–1991
  20. Ugo V, et al. Multiple signaling pathways are involved in erythropoietin-independent differentiation of erythroid progenitors in polycythemia vera. Exp Hematology. 2004;32:179–187
  21. Saharinen P, Takaluoma K, Silvennoinen O. Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol. 2000;20:3387–3395
  22. Luo H, et al. Mutation in the Jak kinase JH2 domain hyperactivates Drosophila and mammalian Jak-Stat pathways. Mol Cell Biol. 1997;17:1562–1571
  23. Hunter T. Signaling - 2000 and beyond. Cell. 2000;100:113–127
  24. Blume-Jensen P, Hunter T. Oncogenic kinase signaling. Nature. 2001;411:355–365
  25. Dai CH, Krantz SB, Sawyer ST. Polycythemia vera V, Enhanced proliferation and phosphorylation due to vanadate are diminished in polycythemia vera erythroid progenitor cells: a possible defect of phosphatase activity in polycythemia vera. Blood. 1997;89:3574–3581
  26. Xu MJ, Sui X, Zhao R, et al. PTP-MEG2 is activated in polycythemia vera erythroid progenitor cells and is required for growth and expansion of erythroid cells. Blood. 2003;102:4354–4360
  27. Neel BG, Gu H, Pao L. The “Shp”ing news: SH2 domain-containing tyrosine phosphatases in cell signaling. Trends Biochem Sci. 2003;28:284–293
  28. Tsui HW, Siminovitch KA, Souza L, Tsui FWL. Motheaten and viable motheaten mice have mutations in the hematopoietic cell phosphatase gene. Nat Genet. 1993;4:124–129
  29. Shultz LD, Schweitzer PA, Rajan TV, et al. Mutations at the murine motheaten locus are within the hematopoietic cell protein tyrosine phosphatase (HCPH) gene. Cell. 1993;73:1445–1454
  30. Prchal JF, Prchal JT. Molecular basis for polycythemia. Curr Opin Hematol. 1999;6:100–109
  31. Klingmuller U, Lorenz U, Cantley LC, et al. Specific recruitment if SH-PTP1 to the erythropoietin receptor causes inactivation of JAK2 and termination of proliferative signals. Cell. 1995;80:729–738
  32. Asimakopoulos FA, Hinshelwood S, Gilbert JG, et al. The gene encoding hematopoietic cell phosphatase (SHP-1) is structurally and transcriptionally intact in polycythemia vera. Oncogene. 1997;14:1215–1222
  33. Anderson P, LeBlanc K, Eriksson B-A, Samuelson J. No evidence for an altered mRNA expression or protein level of hematopoietic cell phosphatase in CD34+ bone marrow progenitor cells or mature peripheral blood cells in polycythemia vera. Eur J Haematol. 1997;59:310–317
  34. Wickrema A, Chen F, Namin F, et al. Defective expression of the SHP-1 phosphatase in polycythemia vera. Exp Hematol. 1999;27:1124–1132
  35. Feng GS. SHP-2 tyrosine phosphatase: signaling one cell or many. Exp Cell Res. 1999;253:47–54
  36. Tartaglia M, Niemeyer CM, Fragale A, et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes, and acute myeloid leukemia. Nat Genet. 2003;34:148–150
  37. Loh ML, Vattikuti S, Schubbert S, et al. Mutations in PTPN11 implicate the SHP-2 phosphatse in leukemogenesis. Blood. 2004;103:2325–2331
  38. Tartaglia M, Martinelli S, Cazzaniga G, et al. Genetic evidence for lineage and differentiation stage related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. Blood. 2004;104:307–313
  39. Bentires-Alj M, Paez JG, David FS, et al. Activating mutations of the Noonan syndrome associated SHP2/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia. Cancer Res. 2004;64:8816–8820
  40. Marine JC, McKay C, Wang D, et al. SOCS3 is essential in the regulation of fetal liver erythropoiesis. Cell. 1999;98:617–627
  41. Sasaki A, Yasukawa H, Souda T, et al. CIS3/SOCS-3 suppresses erythropoietin (Epo) signaling by binding the EPO receptor and JAK2. J Biol Chem. 2000;275:29338–29347
  42. Krebs D, Hilton DJ. SOCS: physiological suppressors of cytokine signaling. J Cell Sci. 2000;113:2813–2819
  43. Steensma DP, Dewald GW, Lasho T, et al. Brief report: the JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both ‘atypical’ myeloproliferative disorders and the myelodysplastic syndrome. Blood 2005; 106: 1207–1212.
  44. Jelinek J, Oki Y, Gharibyan V, et al. JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia-chromosome negative CML, and megakaryocytic leukemia. Blood 2005; 106: 3370–3373.

PII: S1521-6926(05)00090-3

doi: 10.1016/j.beha.2005.07.003

Best Practice & Research Clinical Haematology
Volume 19, Issue 3 , Pages 387-397 , September 2006

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